Interleukin-8 (CXCL8) is a secreted Glu-Leu-Arg (ELR)-positive CXC chemokine produced by macrophages, monocytes, endothelial cells, and epithelial cells in response to bacterial products and pro-inflammatory cytokines. In the extracellular space, CXCL8 binds glycosaminoglycans such as heparan sulfate to establish immobilized haptotactic gradients on endothelial surfaces and engages the Gi-coupled seven-transmembrane receptors CXCR1 (IL8RA) and CXCR2 (IL8RB) on neutrophils and other leukocytes. Receptor activation triggers the interleukin-8-mediated signaling pathway, mobilizing intracellular calcium and driving neutrophil chemotaxis, firm integrin-mediated adhesion, degranulation, and respiratory burst at sites of infection and tissue injury.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001525 angiogenesis | TAS PMID:11483765 Interleukin-8 stimulates human immunodeficiency virus type 1... | MODIFY | Summary: CXCL8 is a secreted chemokine that stimulates endothelial cell proliferation and capillary sprouting as an extracellular regulator rather than executing the morphogenetic machinery of blood vessel formation itself; GOA already captures this role more precisely with GO:0045766 (positive regulation of angiogenesis). Reason: As a secreted signaling ligand, CXCL8 positively regulates angiogenesis via CXCR1/CXCR2 on endothelial cells rather than directly executing blood vessel morphogenesis; refine to GO:0045766 (positive regulation of angiogenesis), which the gene already carries. Proposed replacements: positive regulation of angiogenesis |
| GO:0002237 response to molecule of bacterial origin | IDA PMID:19912257 A20 is an early responding negative regulator of Toll-like r... | KEEP AS NON CORE | Summary: CXCL8 transcription and secretion are strongly induced in epithelial and mucosal tissues upon stimulation with bacterial lipopolysaccharide (PMID:10823949), reflecting its role as an inducible effector of innate bacterial sensing. Reason: Valid inducible upstream response context (corroborated by LPS-induced IL-8 secretion in PMID:10823949; PMID:19912257 is abstract-only in the local cache and foregrounds A20), whereas the direct molecular function of secreted CXCL8 is chemokine receptor activation and neutrophil recruitment. Supporting Evidence: PMID:10823949 Again in human organ cultures from fetuses compared to older children, IL-8 secretion was greater (LPS, 2.5-fold; IL-1beta, 200-fold) and mRNA activity after stimulation was comparably higher, suggesting that increased transcription of the IL-8 gene may account for the excessive response. |
| GO:0005125 cytokine activity | IDA PMID:8399143 Human and bovine granulocyte chemotactic protein-2: complete... | MODIFY | Summary: PMID:8399143 characterizes CXCL8 (IL-8) alongside GCP-2 (CXCL6) as a C-X-C chemokine that induces neutrophil chemotaxis and gelatinase B release; GO:0005125 (cytokine activity) is true but less specific than GO:0008009 (chemokine activity), which is annotated from the same paper. Reason: GO:0005125 (cytokine activity) is an ancestor of GO:0008009 (chemokine activity), which CXCL8 already carries from the same reference (PMID:8399143). Proposed replacements: chemokine activity Supporting Evidence: PMID:8399143 On the basis of the conservation of four cysteine residues, the two molecules are to be classified within the C-X-C chemokine family, including IL-8. |
| GO:0005153 interleukin-8 receptor binding | IPI PMID:1840701 Structure and functional expression of a human interleukin-8... | ACCEPT | Summary: Direct high-affinity binding of human CXCL8 (IL-8) to the cloned human interleukin-8 receptor CXCR1 (UniProtKB:P25024) expressed in mammalian cells, corroborated by NMR and cryo-EM structures of the CXCL8:CXCR1 complex (PMID:29143165; PMID:37433790). Reason: Core receptor-binding activity of CXCL8 toward its cognate receptor CXCR1 (P25024), directly demonstrated in PMID:1840701. Supporting Evidence: PMID:1840701 Mammalian cells transfected with the IL-8 receptor cDNA clone bind IL-8 with high affinity and respond specifically to IL-8 by transiently mobilizing calcium. |
| GO:0005153 interleukin-8 receptor binding | IPI PMID:1840701 Structure and functional expression of a human interleukin-8... | ACCEPT | Summary: Direct binding of human CXCL8 (IL-8) to the human interleukin-8 receptor CXCR2 (UniProtKB:P25025), corroborated by receptor cloning (PMID:1891716) and cryo-EM structures of the CXCL8-activated CXCR2:Gi complex (PMID:32610344). Reason: Core receptor-binding activity of CXCL8 toward its cognate receptor CXCR2 (P25025). Supporting Evidence: PMID:1840701 Mammalian cells transfected with the IL-8 receptor cDNA clone bind IL-8 with high affinity and respond specifically to IL-8 by transiently mobilizing calcium. |
| GO:0005515 protein binding | IPI PMID:10880251 Involvement of alpha-2-macroglobulin receptor in clearance o... | REMOVE | Summary: Generic protein binding annotation for complex formation with alpha-2-macroglobulin (P01023) in alveolar fluid. Reason: Bare GO:0005515 (protein binding) is uninformative per the project protein-binding policy; CXCL8's functional interactions are captured by GO:0005153 (interleukin-8 receptor binding) and GO:0008201 (heparin binding). |
| GO:0005515 protein binding | IPI PMID:22904195 HIV-1 matrix protein p17 promotes angiogenesis via chemokine... | REMOVE | Summary: Generic protein binding annotation for CXCR2 (P25025), where CXCL8 was used as a reference ligand in surface plasmon resonance competition assays with HIV-1 p17. Reason: Bare GO:0005515 (protein binding) is uninformative per the project protein-binding policy and redundant with GO:0005153 (interleukin-8 receptor binding) with P25025. |
| GO:0005515 protein binding | IPI PMID:23597562 Inhibition of tumor angiogenesis and growth by a small-molec... | REMOVE | Summary: Generic protein binding annotation for CXCR2 (P25025) from specificity counter-screening of an FGFR inhibitor. Reason: Bare GO:0005515 (protein binding) is uninformative per the project protein-binding policy and redundant with GO:0005153 (interleukin-8 receptor binding) with P25025. |
| GO:0005515 protein binding | IPI PMID:24501198 TSG-6 inhibits neutrophil migration via direct interaction w... | REMOVE | Summary: Generic protein binding annotation for binding of CXCL8 by the Link module of TSG-6 (TNFAIP6, P98066), which sequesters CXCL8 from endothelial glycosaminoglycans. Reason: Bare GO:0005515 (protein binding) is uninformative per the project protein-binding policy. |
| GO:0005515 protein binding | IPI PMID:26829648 Mycobacterium tuberculosis AtsG (Rv0296c), GlmU (Rv1018c) an... | REMOVE | Summary: Generic protein binding annotation for interaction with Mycobacterium tuberculosis GlmU (P9WGV3). Reason: Bare GO:0005515 (protein binding) is uninformative per the project protein-binding policy. |
| GO:0005515 protein binding | IPI PMID:26829648 Mycobacterium tuberculosis AtsG (Rv0296c), GlmU (Rv1018c) an... | REMOVE | Summary: Generic protein binding annotation for interaction with Mycobacterium tuberculosis proteins. Reason: Bare GO:0005515 (protein binding) is uninformative per the project protein-binding policy. |
| GO:0005515 protein binding | IPI PMID:26829648 Mycobacterium tuberculosis AtsG (Rv0296c), GlmU (Rv1018c) an... | REMOVE | Summary: Generic protein binding annotation for interaction with Mycobacterium tuberculosis AtsG (P9WMN3). Reason: Bare GO:0005515 (protein binding) is uninformative per the project protein-binding policy. |
| GO:0005515 protein binding | IPI PMID:26829648 Mycobacterium tuberculosis AtsG (Rv0296c), GlmU (Rv1018c) an... | REMOVE | Summary: Generic protein binding annotation for interaction with Mycobacterium tuberculosis SahH (Q6MX51). Reason: Bare GO:0005515 (protein binding) is uninformative per the project protein-binding policy. |
| GO:0005515 protein binding | IPI PMID:28381538 Chemokine interactome mapping enables tailored intervention ... | REMOVE | Summary: Generic protein binding annotation for heteromerization with CXCL4/PF4 (P02776). Reason: Bare GO:0005515 (protein binding) is uninformative per the project protein-binding policy. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic propagation from PANTHER node PTN002564680 (PTHR12015 chemokine family) placing secreted CXCL8 activity in the extracellular region. Reason: CXCL8 is synthesized with a 20-residue N-terminal signal peptide and secreted into the extracellular region where it binds glycosaminoglycans and cell-surface CXCR1/CXCR2. |
| GO:0005576 extracellular region | IDA PMID:9568323 Changes in levels of serum IL-8 in burned patients. | ACCEPT | Summary: Immunoassay detection of circulating soluble IL-8 in human serum of burned patients (PMID:9568323). Reason: Directly confirms that mature CXCL8 is secreted into the extracellular region (serum). Supporting Evidence: PMID:9568323 In conclusion, the results showed that there was an increase in serum IL-8 postburn. Serum IL-8 was significantly higher in the septic patients, who all died. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Automated annotation from UniProt subcellular location Secreted (SL-0243) and CXC chemokine InterPro signatures placing CXCL8 in the extracellular region. Reason: Consistent with experimental evidence that CXCL8 is a secreted extracellular chemokine. |
| GO:0005576 extracellular region | TAS PMID:10823949 Inflammation in the developing human intestine: A possible p... | ACCEPT | Summary: Author statement on secreted IL-8 released by intestinal epithelial cells into the extracellular milieu (PMID:10823949). Reason: Consistent with core localization of secreted CXCL8 in the extracellular region. Supporting Evidence: PMID:10823949 Again in human organ cultures from fetuses compared to older children, IL-8 secretion was greater (LPS, 2.5-fold; IL-1beta, 200-fold) and mRNA activity after stimulation was comparably higher, suggesting that increased transcription of the IL-8 gene may account for the excessive response. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-373791 | ACCEPT | Summary: Reactome assertion placing extracellular CXCL8 in the reaction where CXCR1 binds CXCL6 and CXCL8 ligands (R-HSA-373791). Reason: Consistent with core extracellular localization of mature secreted CXCL8. Supporting Evidence: file:genes/human/CXCL8/CXCL8-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-373813 | ACCEPT | Summary: Reactome assertion placing extracellular CXCL8 in the reaction where CXCR2 binds CXC chemokine ligands (R-HSA-373813). Reason: Consistent with core extracellular localization of mature secreted CXCL8. Supporting Evidence: file:genes/human/CXCL8/CXCL8-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-374251 | ACCEPT | Summary: Reactome assertion placing extracellular CXCL8 in complex formation with ACKR1/DARC (R-HSA-374251). Reason: Consistent with core extracellular localization of mature secreted CXCL8. Supporting Evidence: file:genes/human/CXCL8/CXCL8-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-3790137 | ACCEPT | Summary: Reactome assertion placing secreted IL-8 in the extracellular region following senescent cell transcription (R-HSA-3790137). Reason: Consistent with core extracellular localization of mature secreted CXCL8. Supporting Evidence: file:genes/human/CXCL8/CXCL8-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-380073 | ACCEPT | Summary: Reactome assertion placing extracellular CXCL8 in the liganded Gi-activating GPCR complex (R-HSA-380073). Reason: Consistent with core extracellular localization of mature secreted CXCL8. Supporting Evidence: file:genes/human/CXCL8/CXCL8-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-517731 | ACCEPT | Summary: Reactome assertion placing translated and secreted IL-8 in the extracellular region (R-HSA-517731). Reason: Consistent with core extracellular localization of mature secreted CXCL8. Supporting Evidence: file:genes/human/CXCL8/CXCL8-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6784160 | ACCEPT | Summary: Reactome assertion placing secreted CXCL8 in the extracellular region in the IL-10 regulatory pathway (R-HSA-6784160). Reason: Consistent with core extracellular localization of mature secreted CXCL8. Supporting Evidence: file:genes/human/CXCL8/CXCL8-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6789524 | ACCEPT | Summary: Reactome assertion placing secreted CXCL8 in the extracellular region (R-HSA-6789524). Reason: Consistent with core extracellular localization of mature secreted CXCL8. Supporting Evidence: file:genes/human/CXCL8/CXCL8-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749454 | ACCEPT | Summary: Reactome assertion placing extracellular CXCL8 in the dissociating Ligand:GPCR:Gi complex (R-HSA-749454). Reason: Consistent with core extracellular localization of mature secreted CXCL8. Supporting Evidence: file:genes/human/CXCL8/CXCL8-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749456 | ACCEPT | Summary: Reactome assertion placing extracellular CXCL8 in the liganded Gi-activating GPCR complex binding heterotrimeric Gi (R-HSA-749456). Reason: Consistent with core extracellular localization of mature secreted CXCL8. Supporting Evidence: file:genes/human/CXCL8/CXCL8-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted. |
| GO:0006935 chemotaxis | IEA GO_REF:0000002 | MODIFY | Summary: Automated InterPro2GO mapping from InterPro:IPR033899 (Interleukin-8) to general chemotaxis (GO:0006935). Reason: True but less specific than GO:0030593 (neutrophil chemotaxis), which CXCL8 already carries with experimental and phylogenetic evidence. Proposed replacements: neutrophil chemotaxis |
| GO:0006935 chemotaxis | TAS PMID:12782716 An alternatively spliced variant of CXCR3 mediates the inhib... | MODIFY | Summary: Traceable author statement in PMID:12782716 noting ELR-positive CXC chemokines including IL-8 as chemotactic factors; GO:0030593 (neutrophil chemotaxis) is the specific descendant term already present on CXCL8. Reason: True but less specific than GO:0030593 (neutrophil chemotaxis), which CXCL8 already carries. Proposed replacements: neutrophil chemotaxis |
| GO:0006952 defense response | IEA GO_REF:0000002 | MODIFY | Summary: Automated InterPro2GO mapping from InterPro:IPR033899 (Interleukin-8) to broad defense response (GO:0006952). Reason: GO:0006952 (defense response) is true but too general compared to its descendant GO:0006954 (inflammatory response), which CXCL8 already carries. Proposed replacements: inflammatory response |
| GO:0006954 inflammatory response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic propagation from PANTHER node PTN002564680 reflecting the conserved role of chemokines in acute inflammatory responses. Reason: CXCL8 is a major mediator of acute inflammation, while its core biological processes are more specifically captured by GO:0038112 (interleukin-8-mediated signaling pathway), GO:0030593 (neutrophil chemotaxis), and GO:0042119 (neutrophil activation). |
| GO:0006954 inflammatory response | TAS PMID:10823949 Inflammation in the developing human intestine: A possible p... | KEEP AS NON CORE | Summary: PMID:10823949 characterizes IL-8 as a central pro-inflammatory mediator elevated in necrotizing enterocolitis and fetal intestinal inflammation. Reason: Accurate broader physiological process, with the direct cellular programs captured by GO:0038112, GO:0030593, and GO:0042119. Supporting Evidence: PMID:10823949 Again in human organ cultures from fetuses compared to older children, IL-8 secretion was greater (LPS, 2.5-fold; IL-1beta, 200-fold) and mRNA activity after stimulation was comparably higher, suggesting that increased transcription of the IL-8 gene may account for the excessive response. |
| GO:0006954 inflammatory response | TAS PMID:11483765 Interleukin-8 stimulates human immunodeficiency virus type 1... | KEEP AS NON CORE | Summary: Author statement describing IL-8 as a pro-inflammatory chemokine produced during inflammation (PMID:11483765). Reason: Accurate broader physiological process, with the direct cellular programs captured by GO:0038112, GO:0030593, and GO:0042119. Supporting Evidence: PMID:11483765 IL-8 has been demonstrated to attract neutrophils and T cells, stimulate monocyte adherence, and mediate angiogenesis by interacting with the C-X-C chemokine receptors CXCR1 and CXCR2 ( 6 , 22 , 27 , 31 , 47 ). |
| GO:0006955 immune response | IEA GO_REF:0000002 | MODIFY | Summary: Automated InterPro2GO mapping from chemokine InterPro signatures to broad immune response (GO:0006955). Reason: GO:0006955 (immune response) is true of CXCL8 but too general compared to its descendant GO:0042119 (neutrophil activation), which CXCL8 already carries. Proposed replacements: neutrophil activation |
| GO:0007165 signal transduction | TAS PMID:10820279 Differential ability of exogenous chemotactic agents to disr... | MODIFY | Summary: Author statement on IL-8 signaling during neutrophil transendothelial migration (PMID:10820279); GO:0007165 (signal transduction) is too general compared to GO:0038112 (interleukin-8-mediated signaling pathway). Reason: GO:0007165 (signal transduction) is an ancestor of GO:0038112 (interleukin-8-mediated signaling pathway), which CXCL8 already carries. Proposed replacements: interleukin-8-mediated signaling pathway |
| GO:0007186 G protein-coupled receptor signaling pathway | NAS PMID:37433790 Structural basis of CXC chemokine receptor 1 ligand binding ... | MODIFY | Summary: PMID:37433790 reports the cryo-EM structure of CXCL8 bound to CXCR1 and heterotrimeric Gi, directly illustrating the interleukin-8-mediated GPCR signaling complex; GO:0007186 is true but less specific than its descendant GO:0038112 (interleukin-8-mediated signaling pathway). Reason: GO:0007186 (G protein-coupled receptor signaling pathway) is an ancestor of GO:0038112 (interleukin-8-mediated signaling pathway), which CXCL8 already carries. Proposed replacements: interleukin-8-mediated signaling pathway Supporting Evidence: PMID:37433790 Here, we solve the structure of CXCR1 complexed with CXCL8 and cognate G-proteins using cryo-EM, showing the detailed interactions between the receptor, the chemokine and GΞ±i protein. |
| GO:0007186 G protein-coupled receptor signaling pathway | TAS PMID:8381837 IL-8 induces the locomotion of human IL-2-activated natural ... | MODIFY | Summary: PMID:8381837 shows pertussis toxin-sensitive G protein-coupled IL-8 receptor signaling in human NK cells; GO:0007186 is less specific than its descendant GO:0038112 (interleukin-8-mediated signaling pathway). Reason: GO:0007186 (G protein-coupled receptor signaling pathway) is an ancestor of GO:0038112 (interleukin-8-mediated signaling pathway), which CXCL8 already carries. Proposed replacements: interleukin-8-mediated signaling pathway |
| GO:0007204 positive regulation of cytosolic calcium ion concentration | NAS PMID:37433790 Structural basis of CXC chemokine receptor 1 ligand binding ... | KEEP AS NON CORE | Summary: Activation of CXCR1 and CXCR2 by CXCL8 triggers rapid intracellular calcium mobilization via Gi/Gbetagamma-stimulated phospholipase C beta (PMID:1840701; PMID:11877327; PMID:37433790). Reason: Accurate downstream second-messenger sub-process of the interleukin-8-mediated signaling pathway (GO:0038112). Supporting Evidence: PMID:37433790 Formerly named neutrophil-activating factor (NAF)9, it was found to trigger a rapid and transient rise in the cytosolic level of free calcium in neutrophils (but not monocytes, lymphocytes, or platelets) through a GTP-binding protein10. |
| GO:0008009 chemokine activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic propagation from PANTHER node PTN002564680 (PTHR12015 chemokine family), grounded by CXCL8's own experimental annotation (UniProtKB:P10145). Reason: Core molecular function of CXCL8 as the archetypal ELR-positive CXC chemokine. |
| GO:0008009 chemokine activity | IDA PMID:8399143 Human and bovine granulocyte chemotactic protein-2: complete... | ACCEPT | Summary: Direct experimental demonstration in PMID:8399143 that human IL-8 (CXCL8) induces directional chemotaxis and gelatinase B release in human neutrophilic granulocytes. Reason: Core molecular function of CXCL8 directly supported by chemotaxis assays in PMID:8399143. Supporting Evidence: PMID:8399143 On the basis of the conservation of four cysteine residues, the two molecules are to be classified within the C-X-C chemokine family, including IL-8. |
| GO:0008009 chemokine activity | IEA GO_REF:0000002 | ACCEPT | Summary: Automated InterPro2GO mapping from CXC chemokine and Interleukin-8 domain signatures to chemokine activity (GO:0008009). Reason: Consistent with experimental evidence for CXCL8 chemokine activity. |
| GO:0008009 chemokine activity | TAS PMID:10881932 Autocrine growth effect of IL-8 and GROalpha on a human panc... | ACCEPT | Summary: Author statement on IL-8 CXC chemokine activity in PMID:10881932. Reason: Consistent with core chemokine activity of CXCL8. Supporting Evidence: PMID:10881932 A human pancreatic cancer cell line, Capan-1, secretes the chemokines interleukin-8 (IL-8) and growth-related oncogene alpha (GROalpha). |
| GO:0008009 chemokine activity | TAS PMID:12782716 An alternatively spliced variant of CXCR3 mediates the inhib... | ACCEPT | Summary: Author statement on ELR-positive CXC chemokine activity of IL-8 in PMID:12782716. Reason: Consistent with core chemokine activity of CXCL8. Supporting Evidence: PMID:12782716 Chemokines are a family of small, structurally related molecules that regulate cell trafficking of various subsets of leukocytes (1β2). |
| GO:0008201 heparin binding | IDA PMID:24501198 TSG-6 inhibits neutrophil migration via direct interaction w... | ACCEPT | Summary: PMID:24501198 demonstrates direct binding of CXCL8 to heparin and heparan sulfate glycosaminoglycans on endothelial surfaces, which is required for immobilized haptotactic gradient formation and transendothelial neutrophil migration. Reason: Heparin/heparan sulfate glycosaminoglycan binding is a core biochemical activity of CXCL8 required for in vivo presentation to CXCR1/CXCR2 on rolling neutrophils. Supporting Evidence: PMID:24501198 Here we have demonstrated that TSG-6 acts to inhibit CXCL8-induced trans-endothelial migration of human neutrophils via a direct interaction between the TSG-6 Link module and CXCL8, which antagonizes the binding of CXCL8 to heparin/HS. |
| GO:0008285 negative regulation of cell population proliferation | TAS PMID:9551928 CXC chemokines suppress proliferation of myeloid progenitor ... | KEEP AS NON CORE | Summary: PMID:9551928 demonstrates that IL-8 and related CXC chemokines suppress proliferation of human myeloid progenitor cells through activation of CXCR2. Reason: Valid cell-type-specific downstream response mediated by CXCR2 on myeloid progenitors, but secondary to CXCL8's primary role in neutrophil recruitment and activation. Supporting Evidence: PMID:9551928 Our studies are consistent with the idea that IL-8 and MGSA suppress the proliferation of 32D cells by activation of murine CXCR2. |
| GO:0010628 positive regulation of gene expression | IDA PMID:29048659 MicroRNA-520c-3p negatively regulates EMT by targeting IL-8 ... | MARK AS OVER ANNOTATED | Summary: Annotated from PMID:29048659 based on mesenchymal marker (vimentin) changes in breast cancer cell lines when IL-8 is targeted by miR-520c-3p. Reason: Changes in EMT marker expression downstream of autocrine CXCR1/CXCR2 signaling in cancer cells are indirect transcriptional outcomes of receptor signaling rather than a direct gene regulatory role of CXCL8. |
| GO:0010629 negative regulation of gene expression | IDA PMID:29048659 MicroRNA-520c-3p negatively regulates EMT by targeting IL-8 ... | MARK AS OVER ANNOTATED | Summary: Annotated from PMID:29048659 based on E-cadherin downregulation in breast cancer cell lines overexpressing IL-8. Reason: Indirect downstream transcriptional change in an EMT assay rather than a direct gene regulatory function of CXCL8. |
| GO:0016020 membrane | IDA PMID:25411203 Cutting edge: GPR35/CXCR8 is the receptor of the mucosal che... | REMOVE | Summary: Erroneously annotated from PMID:25411203, which identifies the membrane GPCR GPR35/CXCR8 as the receptor for CXCL17 and does not show membrane localization of soluble CXCL8. Reason: CXCL8 is a soluble secreted chemokine lacking transmembrane or lipid-anchor domains, and full text inspection of PMID:25411203 (PMC4355404) confirms the paper characterizes CXCL17 (Q6UXB2) and its membrane receptor GPR35 (Q9HC97, which the authors propose naming CXCR8) rather than CXCL8 (P10145). |
| GO:0019722 calcium-mediated signaling | TAS PMID:11877327 Ca(2+) signalling by recombinant human CXCR2 chemokine recep... | MODIFY | Summary: PMID:11877327 characterizes intracellular Ca2+ mobilization triggered by recombinant human CXCR2 upon IL-8 stimulation in HEK293 cells. Reason: CXCL8 acts as the extracellular receptor agonist initiating interleukin-8-mediated signaling (GO:0038112) and positive regulation of cytosolic calcium ion concentration (GO:0007204), both of which CXCL8 already carries. Proposed replacements: interleukin-8-mediated signaling pathway positive regulation of cytosolic calcium ion concentration Supporting Evidence: PMID:11877327 1. Human embryonic kidney (HEK)-293 cells expressing recombinant G alpha(i)-coupled, human CXC chemokine receptor 2 (CXCR2) were used to study the elevation of the intracellular [Ca(2+)] ([Ca(2+)](i)) in response to interleukin-8 (IL-8) following pre-stimulation of endogenously expressed P2Y1 or P2Y2 nucleotide receptors. |
| GO:0030155 regulation of cell adhesion | IDA PMID:2007144 Chemical synthesis, purification, and characterization of tw... | KEEP AS NON CORE | Summary: PMID:2007144 and PMID:11564821 show that CXCL8 triggers beta2-integrin-dependent neutrophil adhesion to endothelial ligands. Reason: Valid downstream cellular response to CXCR1/CXCR2 signaling during leukocyte arrest, captured more centrally under neutrophil activation (GO:0042119) and neutrophil chemotaxis (GO:0030593). |
| GO:0030593 neutrophil chemotaxis | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic propagation from PANTHER node PTN002564680, grounded by CXCL8's own experimental annotations (UniProtKB:P10145). Reason: Core biological process of CXCL8 as the primary human neutrophil chemoattractant. |
| GO:0030593 neutrophil chemotaxis | IDA PMID:24501198 TSG-6 inhibits neutrophil migration via direct interaction w... | ACCEPT | Summary: PMID:24501198 directly assays CXCL8-induced transendothelial migration and chemotaxis of primary human neutrophils. Reason: Core biological process of CXCL8 directly demonstrated in human neutrophil migration assays. Supporting Evidence: PMID:24501198 Here we have demonstrated that TSG-6 acts to inhibit CXCL8-induced trans-endothelial migration of human neutrophils via a direct interaction between the TSG-6 Link module and CXCL8, which antagonizes the binding of CXCL8 to heparin/HS. |
| GO:0030593 neutrophil chemotaxis | IDA PMID:8399143 Human and bovine granulocyte chemotactic protein-2: complete... | ACCEPT | Summary: PMID:8399143 directly measures human neutrophil chemotactic activity of IL-8 alongside GCP-2 (CXCL6). Reason: Core biological process of CXCL8 supported by direct chemotaxis assays in PMID:8399143. Supporting Evidence: PMID:8399143 We have isolated a new human granulocyte chemotactic protein (GCP-2), coproduced with interleukin-8 (GCP-1/IL-8) by osteosarcoma cells. |
| GO:0030593 neutrophil chemotaxis | IGI PMID:11564821 Immobilized IL-8 triggers progressive activation of neutroph... | ACCEPT | Summary: PMID:11564821 demonstrates that immobilized IL-8 acts with P-selectin and ICAM-1 (P05362) to trigger progressive activation and arrest of rolling human neutrophils under shear flow. Reason: Core biological process of CXCL8 in haptotactic neutrophil recruitment. Supporting Evidence: PMID:11564821 Neutrophils rolled an average of 200 microm on surfaces of P-sel, ICAM-1, and IL-8 before firmly adhering through ICAM-1-beta(2) integrin interactions at 2 dynes/cm(2) wall shear stress. |
| GO:0030593 neutrophil chemotaxis | NAS PMID:37433790 Structural basis of CXC chemokine receptor 1 ligand binding ... | ACCEPT | Summary: Author statement in PMID:37433790 describing CXCL8-driven neutrophil chemotaxis via CXCR1. Reason: Consistent with experimental evidence for CXCL8's core role in neutrophil chemotaxis. Supporting Evidence: PMID:37433790 They are attracted by chemokines to sites of infection and tissue damage, where they kill and phagocytose bacteria. The chemokine CXCL8 (also known as interleukin-8, abbreviated IL-8) and its G-protein-coupled receptors CXCR1 and CXCR2 are crucial elements in this process, and also the development of many cancers. |
| GO:0031623 receptor internalization | IDA PMID:10734056 Regulation of the human chemokine receptor CCR1. Cross-regul... | KEEP AS NON CORE | Summary: PMID:10734056 shows that agonist stimulation of CXCR1 and CXCR2 with IL-8 triggers homologous receptor internalization and arrestin-dependent desensitization. Reason: Agonist-induced CXCR1/CXCR2 internalization is a genuine consequence of ligand binding that terminates receptor signaling, peripheral to the primary activating signaling and chemotactic functions. Supporting Evidence: PMID:10734056 Interleukin-8 stimulation of CXCR1 or CXCR2 cross-phosphorylated CCR1 and cross-desensitized its ability to stimulate GTPase activity and Ca(2+) mobilization. |
| GO:0032642 regulation of chemokine production | NAS PMID:36725964 The chemokines CXCL8 and CXCL12: molecular and functional pr... | MARK AS OVER ANNOTATED | Summary: Annotated from review article PMID:36725964, which discusses transcriptional and post-transcriptional regulation of CXCL8 production itself rather than CXCL8 regulating production of other chemokines. Reason: CXCL8 is the chemokine whose production is regulated in PMID:36725964 rather than a direct regulator of chemokine biosynthesis. |
| GO:0034976 response to endoplasmic reticulum stress | IDA PMID:20829347 Endoplasmic reticulum stress-activated C/EBP homologous prot... | MARK AS OVER ANNOTATED | Summary: PMID:20829347 shows that ER stress-induced CHOP represses PPARgamma and thereby enhances NF-kappaB-dependent IL-8 transcription in intestinal epithelial cells. Reason: CXCL8 is used as a downstream NF-kappaB transcriptional readout of CHOP/PPARgamma signaling during ER stress rather than participating in the endoplasmic reticulum stress response machinery. |
| GO:0035556 intracellular signal transduction | IDA PMID:10734056 Regulation of the human chemokine receptor CCR1. Cross-regul... | MODIFY | Summary: PMID:10734056 assays IL-8-stimulated intracellular calcium mobilization and PLD activation via CXCR1 and CXCR2; as an extracellular ligand, CXCL8 initiates the interleukin-8-mediated signaling pathway (GO:0038112) rather than acting as an intracellular transducer. Reason: Lateral correction: GO:0035556 (intracellular signal transduction) and GO:0007166 (cell surface receptor signaling pathway, ancestor of GO:0038112) are sibling branches under GO:0007165 (signal transduction). Because CXCL8 is the secreted extracellular ligand that engages cell-surface CXCR1/CXCR2 rather than an intracellular signaling protein, replace GO:0035556 with GO:0038112 (interleukin-8-mediated signaling pathway), which CXCL8 already carries. Proposed replacements: interleukin-8-mediated signaling pathway |
| GO:0038112 interleukin-8-mediated signaling pathway | IDA PMID:8399143 Human and bovine granulocyte chemotactic protein-2: complete... | ACCEPT | Summary: PMID:8399143 demonstrates that IL-8 activates specific neutrophil receptor and post-receptor signaling mechanisms driving chemotaxis and gelatinase B release, corroborated by receptor cloning (PMID:1840701; PMID:1891716) and cryo-EM structures of CXCL8-bound CXCR1:Gi and CXCR2:Gi signaling complexes (PMID:32610344; PMID:37433790). Reason: Canonical pathway-level biological process directly initiated by CXCL8 engagement of CXCR1 and CXCR2. Supporting Evidence: PMID:8399143 Both chemokines can also activate postreceptor mechanisms leading to release of gelatinase B by granulocytes. |
| GO:0042119 neutrophil activation | IDA PMID:11564821 Immobilized IL-8 triggers progressive activation of neutroph... | ACCEPT | Summary: PMID:11564821 directly demonstrates that immobilized IL-8 triggers progressive activation, pseudopod formation, and beta2-integrin-mediated arrest of rolling human neutrophils. Reason: Core biological process of CXCL8 in activating human neutrophils. Supporting Evidence: PMID:11564821 Immobilized IL-8 triggers progressive activation of neutrophils rolling in vitro on P-selectin and intercellular adhesion molecule-1. |
| GO:0042119 neutrophil activation | IDA PMID:8399143 Human and bovine granulocyte chemotactic protein-2: complete... | ACCEPT | Summary: PMID:8399143 shows that IL-8 triggers granulocyte degranulation (gelatinase B release) in addition to chemotaxis. Reason: Core biological process of CXCL8 supported by direct granulocyte activation assays in PMID:8399143. Supporting Evidence: PMID:8399143 Both chemokines can also activate postreceptor mechanisms leading to release of gelatinase B by granulocytes. |
| GO:0042119 neutrophil activation | NAS PMID:37433790 Structural basis of CXC chemokine receptor 1 ligand binding ... | ACCEPT | Summary: Author statement in PMID:37433790 describing CXCL8-triggered neutrophil activation and oxidative burst. Reason: Consistent with experimental evidence for CXCL8's core role in neutrophil activation. Supporting Evidence: PMID:37433790 Formerly named neutrophil-activating factor (NAF)9, it was found to trigger a rapid and transient rise in the cytosolic level of free calcium in neutrophils (but not monocytes, lymphocytes, or platelets) through a GTP-binding protein10. |
| GO:0042119 neutrophil activation | TAS PMID:11483765 Interleukin-8 stimulates human immunodeficiency virus type 1... | ACCEPT | Summary: Author statement in PMID:11483765 noting IL-8 as a neutrophil-activating chemokine. Reason: Consistent with experimental evidence for CXCL8's core role in neutrophil activation. Supporting Evidence: PMID:11483765 IL-8 has been demonstrated to attract neutrophils and T cells, stimulate monocyte adherence, and mediate angiogenesis by interacting with the C-X-C chemokine receptors CXCR1 and CXCR2 ( 6 , 22 , 27 , 31 , 47 ). |
| GO:0044344 cellular response to fibroblast growth factor stimulus | IEP PMID:9407497 Lymphocyte-derived cytokines induce sequential expression of... | KEEP AS NON CORE | Summary: Annotated from expression profiling in PMID:9407497 examining cytokine-induced chemokine expression in human mesangial cells. Reason: Upstream transcriptional induction context (IEP) rather than a core function of the mature CXCL8 protein. |
| GO:0045091 regulation of single stranded viral RNA replication via double stranded DNA intermediate | IDA PMID:11483765 Interleukin-8 stimulates human immunodeficiency virus type 1... | KEEP AS NON CORE | Summary: PMID:11483765 shows that exogenous IL-8 stimulates HIV-1 replication in human macrophages and T lymphocytes via CXCR1 and CXCR2. Reason: Pathogen-specific downstream consequence of CXCR1/CXCR2 signaling in HIV-1-infected cells, peripheral to CXCL8's core physiological functions. Supporting Evidence: PMID:11483765 Here we demonstrate that IL-8 also stimulates HIV-1 replication in macrophages and T lymphocytes. |
| GO:0045236 CXCR chemokine receptor binding | IBA GO_REF:0000033 | MODIFY | Summary: Phylogenetic propagation from PANTHER node PTN002564680 for CXCR chemokine receptor binding; for CXCL8, the specific child term GO:0005153 (interleukin-8 receptor binding) is directly supported and already present. Reason: GO:0045236 (CXCR chemokine receptor binding) is an ancestor of GO:0005153 (interleukin-8 receptor binding), which CXCL8 already carries with direct experimental support for CXCR1 and CXCR2. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: interleukin-8 receptor binding |
| GO:0045236 CXCR chemokine receptor binding | IDA PMID:25411203 Cutting edge: GPR35/CXCR8 is the receptor of the mucosal che... | MODIFY | Summary: PMID:25411203 identifies GPR35/CXCR8 as the receptor for CXCL17 (not CXCL8); however, the claim that CXCL8 binds CXCR chemokine receptors is true and is more specifically captured on CXCL8 by GO:0005153 (interleukin-8 receptor binding). Reason: Although PMID:25411203 is about CXCL17-CXCR8 rather than CXCL8, the term GO:0045236 (CXCR chemokine receptor binding) is true for CXCL8 and is refined to its specific child term GO:0005153 (interleukin-8 receptor binding), which CXCL8 already carries. Proposed replacements: interleukin-8 receptor binding |
| GO:0045730 respiratory burst | NAS PMID:37433790 Structural basis of CXC chemokine receptor 1 ligand binding ... | KEEP AS NON CORE | Summary: Author statement in PMID:37433790 noting that CXCL8 activation of CXCR1 triggers the neutrophil oxidative burst. Reason: Valid downstream effector response of CXCL8-activated neutrophils, subsumed under the core cellular program of neutrophil activation (GO:0042119). Supporting Evidence: PMID:37433790 Formerly named neutrophil-activating factor (NAF)9, it was found to trigger a rapid and transient rise in the cytosolic level of free calcium in neutrophils (but not monocytes, lymphocytes, or platelets) through a GTP-binding protein10. |
| GO:0045744 negative regulation of G protein-coupled receptor signaling pathway | IDA PMID:10734056 Regulation of the human chemokine receptor CCR1. Cross-regul... | KEEP AS NON CORE | Summary: PMID:10734056 demonstrates that activation of CXCR1 and CXCR2 by IL-8 induces heterologous desensitization (cross-phosphorylation and inhibition) of the chemokine receptor CCR1. Reason: Real cross-desensitization phenomenon downstream of CXCR1/CXCR2 activation, secondary to CXCL8's primary agonist function in the interleukin-8-mediated signaling pathway (GO:0038112). Supporting Evidence: PMID:10734056 Interleukin-8 stimulation of CXCR1 or CXCR2 cross-phosphorylated CCR1 and cross-desensitized its ability to stimulate GTPase activity and Ca(2+) mobilization. |
| GO:0045766 positive regulation of angiogenesis | IDA PMID:19035451 CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote inva... | KEEP AS NON CORE | Summary: PMID:19035451 demonstrates that recombinant CXCL8 promotes human umbilical vein endothelial cell (HUVEC) migration, invasion, and tube formation in vitro. Reason: Well-established pro-angiogenic activity of ELR-positive CXC chemokines via endothelial CXCR2, distinct from CXCL8's primary immune function in neutrophil chemotaxis and activation. Supporting Evidence: PMID:19035451 CXCL8 enhanced proliferation/invasion of HUVECs but did not promote proliferation/invasion of PaCa. Both recombinant and PaCa-derived CXCL8 enhanced tube formation of HUVECs that were co-cultured with fibroblast cells. |
| GO:0048566 embryonic digestive tract development | IEP PMID:20875417 TGF-Ξ²2 suppresses macrophage cytokine production and mucosal... | MARK AS OVER ANNOTATED | Summary: Annotated from IEP in PMID:20875417 because CXCL8 levels were measured in developing fetal intestinal macrophages treated with TGF-beta2. Reason: Expression of an inflammatory chemokine in fetal intestinal macrophages does not indicate that CXCL8 participates in embryonic digestive tract morphogenesis. |
| GO:0050920 regulation of chemotaxis | NAS PMID:37433790 Structural basis of CXC chemokine receptor 1 ligand binding ... | MODIFY | Summary: Non-traceable author statement in PMID:37433790; CXCL8 is the chemoattractant itself that directly drives neutrophil chemotaxis (GO:0030593). Reason: CXCL8 directly executes neutrophil chemotaxis (GO:0030593), which is already annotated from the same reference and experimental papers. Proposed replacements: neutrophil chemotaxis |
| GO:0050930 induction of positive chemotaxis | IGI PMID:11564821 Immobilized IL-8 triggers progressive activation of neutroph... | MODIFY | Summary: Annotated alongside GO:0030593 from PMID:11564821 for immobilized IL-8 acting on rolling human neutrophils. Reason: As the chemoattractant ligand itself, CXCL8's role is best captured directly by GO:0030593 (neutrophil chemotaxis), which is already annotated from PMID:11564821. Proposed replacements: neutrophil chemotaxis |
| GO:0060354 negative regulation of cell adhesion molecule production | IDA PMID:29048659 MicroRNA-520c-3p negatively regulates EMT by targeting IL-8 ... | MARK AS OVER ANNOTATED | Summary: Annotated from PMID:29048659 based on E-cadherin expression changes in breast cancer cells upon miR-520c-3p/IL-8 manipulation. Reason: Indirect downstream change in E-cadherin levels during tumour cell EMT rather than a direct regulatory function of CXCL8. |
| GO:0061844 antimicrobial humoral immune response mediated by antimicrobial peptide | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic propagation from PANTHER node PTN002564680 (seeded in part by UniProtKB:P10145) reflecting the direct microbicidal activity of the cationic C-terminal alpha-helix (and proteolytic fragment) of CXCL8 and related kinocidins. Reason: Secondary antimicrobial peptide (kinocidin) activity of CXCL8, distinct from its primary receptor-mediated chemokine signaling function. |
| GO:0071222 cellular response to lipopolysaccharide | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic propagation from PANTHER node PTN002564680 reflecting strong induction of CXCL8 and related chemokines in response to bacterial lipopolysaccharide. Reason: Valid upstream induction context, whereas the direct molecular function of secreted CXCL8 is chemokine receptor activation and neutrophil chemotaxis. |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:19912257 A20 is an early responding negative regulator of Toll-like r... | KEEP AS NON CORE | Summary: PMID:19912257 measures IL-8 secretion by intestinal epithelial cells in response to bacterial PAMPs including LPS and flagellin. Reason: Valid upstream induction context, peripheral to the direct receptor-activating function of the secreted chemokine. |
| GO:0071347 cellular response to interleukin-1 | IEP PMID:9407497 Lymphocyte-derived cytokines induce sequential expression of... | KEEP AS NON CORE | Summary: PMID:9407497 shows that IL-1beta strongly induces IL-8 mRNA expression and protein secretion in human mesangial cells. Reason: Upstream transcriptional induction context (IEP) rather than a direct biochemical function of secreted CXCL8. Supporting Evidence: PMID:9407497 Finally, unlike other mesangial growth factors basic fibroblast growth factor (bFGF) induced MCP-1, RANTES, and IL-8 mRNA expression, suggesting an involvement of autocrine regulation mechanisms in mesangial chemokine expression. |
| GO:0071356 cellular response to tumor necrosis factor | IEP PMID:9407497 Lymphocyte-derived cytokines induce sequential expression of... | KEEP AS NON CORE | Summary: PMID:9407497 shows that TNF-alpha strongly induces IL-8 mRNA expression and protein secretion in human mesangial cells. Reason: Upstream transcriptional induction context (IEP) rather than a direct biochemical function of secreted CXCL8. Supporting Evidence: PMID:9407497 Finally, unlike other mesangial growth factors basic fibroblast growth factor (bFGF) induced MCP-1, RANTES, and IL-8 mRNA expression, suggesting an involvement of autocrine regulation mechanisms in mesangial chemokine expression. |
| GO:0090023 positive regulation of neutrophil chemotaxis | TAS PMID:1699135 Selective attraction of monocytes and T lymphocytes of the m... | MODIFY | Summary: Traceable author statement in PMID:1699135 using IL-8 as a control neutrophil chemoattractant; CXCL8 directly executes neutrophil chemotaxis (GO:0030593). Reason: As the chemoattractant ligand that forms the chemotactic gradient, CXCL8 directly mediates neutrophil chemotaxis (GO:0030593), which it already carries. Proposed replacements: neutrophil chemotaxis |
| GO:0097648 G protein-coupled receptor complex | IPI PMID:29143165 Structure of monomeric Interleukin-8 and its interactions wi... | ACCEPT | Summary: Solution NMR characterization of monomeric CXCL8 bound to the N-terminal binding site-I of human CXCR1 in membrane-mimetic environments (PMID:29143165). Reason: CXCL8 is a direct structural component of the agonist-bound CXCR1/CXCR2 GPCR signaling complex. Supporting Evidence: PMID:29143165 The structure of monomeric human chemokine IL-8 (residues 1-66) was determined in aqueous solution by NMR spectroscopy. |
| GO:0097648 G protein-coupled receptor complex | IPI PMID:32610344 Structural basis of CXC chemokine receptor 2 activation and ... | ACCEPT | Summary: Cryo-EM structures of human CXCL8 bound to CXCR2 in complex with heterotrimeric Gi protein (PMID:32610344). Reason: Directly resolves CXCL8 as an integral subunit of the active CXCL8:CXCR2:Gi GPCR signaling complex. Supporting Evidence: PMID:32610344 Here we present the cryo-electron microscopy structures of interleukin-8 (IL-8, also known as CXCL8)-activated human CXC chemokine receptor 2 (CXCR2) in complex with Gi protein, along with a crystal structure of CXCR2 bound to a designed allosteric antagonist. |
| GO:0097648 G protein-coupled receptor complex | IPI PMID:36725964 The chemokines CXCL8 and CXCL12: molecular and functional pr... | ACCEPT | Summary: Review of structural and biochemical evidence for CXCL8 complexes with CXCR1, CXCR2, and ACKR1 (PMID:36725964). Reason: Consistent with cryo-EM and NMR structures of CXCL8-bound GPCR complexes. Supporting Evidence: PMID:36725964 CXCL8 activity inherently depends on interaction with the human CXC chemokine receptors CXCR1 and CXCR2, the atypical chemokine receptor ACKR1, and glycosaminoglycans. |
| GO:2000535 regulation of entry of bacterium into host cell | IMP PMID:26829648 Mycobacterium tuberculosis AtsG (Rv0296c), GlmU (Rv1018c) an... | KEEP AS NON CORE | Summary: PMID:26829648 shows that Mycobacterium tuberculosis surface proteins AtsG, GlmU, and SahH bind human IL-8 to promote bacterial entry into human neutrophils. Reason: Pathogen subversion of host CXCL8 during mycobacterial infection, peripheral to CXCL8's endogenous signaling function. Supporting Evidence: PMID:26829648 Mycobacterium tuberculosis AtsG (Rv0296c), GlmU (Rv1018c) and SahH (Rv3248c) Proteins Function as the Human IL-8-Binding Effectors and Contribute to Pathogen Entry into Human Neutrophils. |
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Download this section (compressed HTML)Q: How do the tissue-predominant 77-amino-acid (endothelial) and 72-amino-acid (leukocyte) N-terminal proteolytic isoforms of CXCL8 differ in their in vivo partitioning between monomer and dimer states on endothelial heparan sulfate proteoglycans during neutrophil extravasation?
Suggested experts: Krishna Rajarathnam, Tracy M. Handel, Paul Proost
Experiment: Perform time-resolved cryo-EM and single-molecule FRET on CXCR1 and CXCR2 reconstituted in lipid nanodiscs with monomeric versus dimeric CXCL8 (72-aa and 77-aa variants) and defined heparan sulfate oligosaccharides to determine how glycosaminoglycan co-engagement shapes Gi versus beta-arrestin coupling bias.
Hypothesis: Monomeric 72-aa CXCL8 preferentially stabilizes the canonical Gi-coupled active state of both CXCR1 and CXCR2, whereas dimeric and 77-aa CXCL8 shift receptor conformational equilibria toward differential beta-arrestin recruitment and receptor internalization.
Type: Cryo-EM and single-molecule FRET signaling bias assay
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