SCGB1A1 (Club Cell Secretory Protein/Clara Cell 10-kDa Protein) – Function and Localization OpenAI o3-deep-research-2025-06-26 73 citations 2025-11-03T22:18:05.681853

SCGB1A1 (Club Cell Secretory Protein/Clara Cell 10-kDa Protein) – Function and Localization

Gene and Protein Overview

SCGB1A1 (Secretoglobin Family 1A Member 1) is a small secreted protein best known as Club Cell Secretory Protein (CCSP), formerly called Clara Cell 10-kDa protein (CC10/CC16) or uteroglobin. It belongs to the secretoglobin superfamily – a group of small, secreted, dimeric proteins (pmc.ncbi.nlm.nih.gov). The mature SCGB1A1 protein is a homodimer (~15–16 kDa total) composed of two identical subunits. Each monomer is ~70–90 amino acids long (after signal peptide cleavage) and together they form a stable dimer with an internal hydrophobic cavity (pubmed.ncbi.nlm.nih.gov). This internal pocket at the dimer interface allows SCGB1A1 to bind small hydrophobic ligands (pubmed.ncbi.nlm.nih.gov). The protein contains key structural residues (e.g. Lys-43 and Asp-46 in human SCGB1A1) that are critical for its functional interactions (pmc.ncbi.nlm.nih.gov). SCGB1A1 has no known enzymatic activity; rather, its function is mediated by binding to other molecules and modulating their activity.

Expression and Localization

SCGB1A1 is predominantly produced by club cells (Clara cells) in the bronchiolar airways of the lung, making it one of the most abundant proteins in the lung airways (pubmed.ncbi.nlm.nih.gov). It is also expressed by epithelial cells in other mucosal tissues, such as the uterus and nasopharynx, albeit at lower levels (journals.plos.org) (pubmed.ncbi.nlm.nih.gov). In the lung, SCGB1A1 is stored in secretory granules of club cells and actively secreted into the airway lining fluid. Baseline levels in bronchoalveolar fluid are high, and the protein is detectable in the circulation (blood) and even in urine under normal conditions (pubmed.ncbi.nlm.nih.gov). This reflects its abundance and stability as a secreted protein. Notably, SCGB1A1 is an extracellular protein – it carries out its functions in the lung lining fluid and extracellular spaces rather than inside cells. It can also diffuse or be transported into the bloodstream, which has made it useful as a biomarker of lung epithelial integrity (low serum levels often correlate with lung injury or club cell loss) (pubmed.ncbi.nlm.nih.gov).

Primary Function and Biochemical Activity

SCGB1A1’s primary role is immunomodulatory and anti-inflammatory, particularly in the lung airways. It is often described as a natural anti-inflammatory protein secreted by airway epithelium (pubmed.ncbi.nlm.nih.gov). Unlike enzymes or receptors, SCGB1A1 acts by binding and sequestering specific ligands and proteins involved in inflammation. A key target is Phospholipase A₂ (PLA₂), an enzyme that releases arachidonic acid from membrane phospholipids to generate pro-inflammatory eicosanoids. SCGB1A1 directly binds to and inactivates secretory PLA₂, thereby preventing the downstream production of arachidonic acid metabolites like leukotrienes and prostaglandins (journals.plos.org). Mutagenesis studies (e.g. replacing Lys-43 or Asp-46) abolish PLA₂ inhibition, confirming that SCGB1A1’s interaction with PLA₂ is specific and structurally mediated (pmc.ncbi.nlm.nih.gov). By inhibiting PLA₂, SCGB1A1 limits the generation of neutrophil-activating lipid mediators, which is thought to reduce acute lung inflammation and tissue injury (such as in ARDS) (journals.plos.org).

In addition to PLA₂, SCGB1A1 binds various hydrophobic inflammatory mediators. For example, it can sequester certain prostaglandins – studies have shown it binds and neutralizes prostaglandin D₂ and F₂α, blocking their interaction with their G-protein coupled receptors (pmc.ncbi.nlm.nih.gov). By buffering these prostanoids, SCGB1A1 prevents prostaglandin-induced pro-inflammatory gene expression in the airway. Mandal et al. (2004) demonstrated that uteroglobin (SCGB1A1) addition repressed allergen-induced inflammation by blocking PGD₂ receptor signaling in a mouse asthma model (pmc.ncbi.nlm.nih.gov). Similarly, it was reported that SCGB1A1 can interfere with PGF₂α receptor–mediated responses (pmc.ncbi.nlm.nih.gov). These findings indicate that SCGB1A1 acts as a “decoy” or scavenger for inflammatory ligands, reducing their ability to trigger immune cells.

SCGB1A1’s anti-inflammatory scope also extends to cytokines and chemokines. It has been shown to bind certain pro-inflammatory cytokines, effectively sequestering them (journals.plos.org). This contributes to its ability to interfere with leukocyte chemotaxis and recruitment (journals.plos.org). For instance, in experimental models lacking SCGB1A1, there is excessive recruitment of neutrophils to the airways in response to irritants or infection, whereas presence of SCGB1A1 restrains this neutrophilic influx (pubmed.ncbi.nlm.nih.gov) (journals.plos.org). SCGB1A1 can even be taken up by immune cells: immuno-electron microscopy studies detected SCGB1A1 inside neutrophils in inflamed lungs, suggesting direct protein-leukocyte interaction (journals.plos.org). Inside these cells, SCGB1A1 might modulate their function (potentially by affecting signaling pathways or reactive oxygen species production (journals.plos.org)).

Notably, SCGB1A1 also modulates intracellular signaling in immune and epithelial cells. It has been shown to inhibit NF-κB activation in airway epithelial cells, thus down-regulating the transcription of many inflammatory genes (pmc.ncbi.nlm.nih.gov). A study in human airway cells demonstrated that overexpression of CC10/SCGB1A1 suppresses NF-κB nuclear translocation and activity, thereby reducing cytokine production (pmc.ncbi.nlm.nih.gov). Consistent with this, exogenous SCGB1A1 protein dampens macrophage activation: a 2020 study added recombinant SCGB1A1 to cultured primary alveolar macrophages and found significantly blunted release of key cytokines (IL-1β, IL-6, IL-8, TNF-α, MIP-1α, MCP-1) in response to bacterial stimuli (pmc.ncbi.nlm.nih.gov). This blunting of macrophage inflammatory responses illustrates how SCGB1A1 acts as a brake on the lung’s immune system to prevent overreaction. Collectively, these mechanisms – inhibition of PLA₂ and NF-κB, sequestration of eicosanoids and cytokines, and blocking of chemoattractant signals – explain SCGB1A1’s core function as an anti-inflammatory guardian in the airways (journals.plos.org) (pmc.ncbi.nlm.nih.gov).

Biological Processes and Pathways

Through the above interactions, SCGB1A1 participates in several biological processes: chiefly regulation of inflammatory response, airway immune homeostasis, and tissue repair. In the eicosanoid pathway, SCGB1A1’s inhibition of PLA₂ means that upstream steps of prostaglandin and leukotriene synthesis are curtailed (journals.plos.org). This reduces activation of cells like neutrophils and eosinophils that respond to those lipid mediators. In parallel, by binding prostaglandins and blocking their receptors, SCGB1A1 directly dampens prostaglandin-signaling pathways that would otherwise lead to bronchoconstriction, vasodilation, and immune cell recruitment (pmc.ncbi.nlm.nih.gov). Thus, SCGB1A1 inserts itself into the arachidonic acid cascade as a negative regulator.

SCGB1A1 also influences chemokine and cytokine signaling networks in the lung. Its ability to reduce IL-8, TNF-α and other cytokine output from macrophages and epithelial cells means pathways like the NF-κB pathway and MAPK pathways (which control cytokine gene expression) are kept in check (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In effect, SCGB1A1 elevates the threshold for lung inflammation by requiring a stronger stimulus to overcome its inhibitory presence. It contributes to maintaining an anti-inflammatory bias in the steady state lung environment (sometimes described as keeping alveolar macrophages in a “quiescent” state) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Another process involving SCGB1A1 is fibrosis and tissue remodeling. Chronic inflammation often leads to fibrotic changes; by suppressing chronic inflammatory signals, SCGB1A1 indirectly has anti-fibrotic effects (pmc.ncbi.nlm.nih.gov). For example, SCGB1A1 deficiency in mice has been linked to heightened TGF-β and collagen deposition after lung injury, whereas presence of SCGB1A1 mitigates such profibrotic pathways (pmc.ncbi.nlm.nih.gov). SCGB1A1 has even been reported to inhibit fibroblast migration in vitro via a PLA₂-dependent mechanism (pmc.ncbi.nlm.nih.gov), suggesting it can influence repair processes.

It’s important to note that SCGB1A1 does not function as a classical signaling ligand with a dedicated receptor. Despite being a secreted protein, no specific high-affinity SCGB1A1 receptor has been definitively identified on target cells. Instead, SCGB1A1’s “signaling” role is more akin to a buffer or modulator: it binds inflammatory mediators (lipids, cytokines, chemoattractants) and possibly coats cell surfaces, thereby broadly altering signaling thresholds. In summary, SCGB1A1 operates at the interface of innate immune pathways – intercepting inflammatory triggers upstream and reinforcing endogenous anti-inflammatory signaling (such as by preventing NF-κB activation). This positions SCGB1A1 as a key regulator of the airway inflammatory cascade and surfactant homeostasis.

Experimental Evidence and Clinical Relevance

Experimental models strongly support SCGB1A1’s functional role: Mice genetically knocked out for Scgb1a1 exhibit exaggerated pulmonary inflammation when challenged. Mandal et al. reported that UG/SCGB1A1-knockout mice show heightened eosinophilic inflammation and Th2 cytokine production in asthma models, underscoring the protein’s role in restraining allergic inflammation (pubmed.ncbi.nlm.nih.gov). Conversely, mice or cells supplemented with exogenous SCGB1A1 have reduced inflammatory responses, as noted in macrophage studies and in in vivo lung injury models (pmc.ncbi.nlm.nih.gov) (journals.plos.org). For instance, overexpressing SCGB1A1 in mouse airways was shown to protect against ventilator-induced lung injury and decrease cytokine levels in bronchoalveolar fluid (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These controlled experiments give confidence that SCGB1A1 is not just a correlated marker but a causal modulator of lung inflammation.

Clinically, SCGB1A1 (often measured as CC16 in serum or sputum) has been linked to lung disease states. Asthma and COPD patients generally have lower airway SCGB1A1 levels, correlating with greater inflammation (journals.plos.org) (pubmed.ncbi.nlm.nih.gov). The protein is often depleted in the bronchiolar epithelium and bronchoalveolar fluid of asthmatics, presumably due to club cell damage or downregulation in chronic inflammation (journals.plos.org). This deficiency may remove an important brake on inflammation, potentially exacerbating disease severity. On the other hand, certain restrictive lung diseases (pulmonary fibrosis, etc.) show elevated SCGB1A1 levels in lung fluid and blood, which might reflect a compensatory upregulation or leakage from injured epithelium (pubmed.ncbi.nlm.nih.gov). Such observations support SCGB1A1’s role in human pulmonary homeostasis. Additionally, outside the lung, SCGB1A1’s anti-inflammatory action has been observed – for example, administering recombinant human uteroglobin reduced kidney inflammation in a mouse glomerulonephritis model (journals.plos.org), suggesting a broader therapeutic potential.

Therapeutic and real-world applications: Because of its protective effects, SCGB1A1 is being explored as a treatment and a biomarker. In neonatology, recombinant human CC10 (rhCC10) has been tested in premature infants at risk of bronchopulmonary dysplasia, with early trials indicating it can be safely given intratracheally and may reduce inflammation in the lung (pubmed.ncbi.nlm.nih.gov). More broadly, researchers view SCGB1A1 as a prototype anti-inflammatory agent. An Annual Review of Medicine in 2023 highlighted that “recent studies demonstrate multiple mechanisms by which CCSP dampens acute and chronic lung inflammation” and that augmenting CCSP could be a novel therapeutic strategy for lung diseases (pubmed.ncbi.nlm.nih.gov). There is interest in boosting SCGB1A1 levels (e.g. via inhaled recombinant protein or drugs that induce its expression) in diseases like COPD, asthma, and acute lung injury. Glucocorticoid steroids, a standard asthma therapy, are known to increase SCGB1A1 expression, which might partly mediate their benefit (geneglobe.qiagen.com). Thus, SCGB1A1 sits at a strategic point in pulmonary medicine – as a biomarker of epithelial health, a target for therapy, and a clue to the lung’s intrinsic anti-inflammatory defenses.

Conclusion and Expert Perspectives

SCGB1A1 (uteroglobin/CCSP) is now recognized as a critical endogenous anti-inflammatory protein in humans. By operating in the extracellular space of the lung and other mucosal organs, it binds pro-inflammatory molecules (like PLA₂ enzymes and prostaglandins) and prevents excessive immune activation (journals.plos.org) (pmc.ncbi.nlm.nih.gov). Its role is distinct from classic cytokines: rather than triggering immune responses, it tones them down, promoting resolution and protecting tissues from collateral damage. Experts in pulmonary biology regard SCGB1A1 as a key factor in maintaining airway homeostasis and preventing chronic inflammation (pubmed.ncbi.nlm.nih.gov) (journals.plos.org). Ongoing research (2020–2024) continues to uncover new facets – such as SCGB1A1’s influence on macrophage polarization, its potential anti-viral properties, and its regulation by signaling pathways like FOXA2/FOXP (transcription factors controlling club cell function) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

In summary, SCGB1A1’s primary function is to safeguard mucosal tissues by curbing inflammation. It does so via a combination of biochemical mechanisms: inhibiting PLA₂ and arachidonate metabolism, binding inflammatory lipids and cytokines, and modulating immune cell behavior (journals.plos.org) (pmc.ncbi.nlm.nih.gov). Localization in secretory club cells and secretion into airway fluids positions it exactly where these inflammatory processes occur, ensuring timely intervention at the lung interface. Given its significant regulatory role, SCGB1A1 continues to be studied as both a diagnostic marker of lung injury and a therapeutic candidate to treat inflammatory and fibrotic diseases (pubmed.ncbi.nlm.nih.gov). The convergence of biochemical, structural, and animal model evidence paints a consistent picture: SCGB1A1 is a pivotal anti-inflammatory “guardian” of the airway, contributing to healthy pulmonary function by keeping immune responses in balance (pubmed.ncbi.nlm.nih.gov) (journals.plos.org).

References:

  1. Côté O. et al. (2014). PLOS ONE 9(4): e96217 – “Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil ROS Production, Phagocytosis and NET Formation.” DOI:10.1371/journal.pone.0096217 (journals.plos.org) (journals.plos.org).
  2. Xu M. et al. (2020). Front. Immunol. 11:584310 – “Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity.” Published Oct 1, 2020 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).
  3. Mandal A.K. et al. (2004). J. Exp. Med. 199(10):1317–1330 – “Uteroglobin represses allergen-induced inflammatory response by blocking PGD₂ receptor–mediated functions.” DOI:10.1084/jem.20031666 (pmc.ncbi.nlm.nih.gov).
  4. Chowdhury B. et al. (2002). Biochem. Biophys. Res. Commun. 295(4):877–883 – “Lys-43 and Asp-46 in uteroglobin are essential for its phospholipase A₂ inhibitory activity.” DOI:10.1016/S0006-291X(02)00767-2 (pmc.ncbi.nlm.nih.gov).
  5. Lesur O. et al. (1995). Am. J. Respir. Crit. Care Med. 152(1):290–297 – “Clara cell protein (CC-16) induces a PLA₂-mediated inhibition of fibroblast migration in vitro.” DOI:10.1164/ajrccm.152.1.7541278 (pmc.ncbi.nlm.nih.gov).
  6. Martinu T. et al. (2023). Annu. Rev. Med. 74:193–208 – “Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics.” (Published Feb 2023) (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov).
  7. “Secretoglobin (SCGB) superfamily is a group of small, secreted, dimeric proteins…” – Amatngalim GD et al., Cytokine (2018) (cited in (pmc.ncbi.nlm.nih.gov)).
  8. “UG is an anti-inflammatory protein secreted by epithelia of organs with external contact…” – Asim Mandal et al., J. Exp. Med. (May 2004) (pubmed.ncbi.nlm.nih.gov).
  9. “SCGB1A1 binds small–medium ligands through an internal hydrophobic cavity at the dimer interface.” – Blaas L. et al., FEBS J. (2001) (cited in (pubmed.ncbi.nlm.nih.gov)).
  10. “Exogenous SCGB1A1 blunts release of IL-1β, IL-6, IL-8, TNF-α, etc., mitigating cytokine surges in lungs.” – Xu M. et al., Front. Immunol. (2020) (pmc.ncbi.nlm.nih.gov).

Citations

  1. AnnotationURLCitation(end_index=537, start_index=424, title='The cytokine-driven regulation of secretoglobins in normal human upper airway and their expression, particularly that of uteroglobin-related protein 1, in chronic rhinosinusitis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3063214/#:~:text=Secretoglobin%20,Clara%20cell')
  2. AnnotationURLCitation(end_index=906, start_index=782, title='The uteroglobin fold - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11193783/#:~:text=medium,the%20cap%20domain%20of%20Xanthobacter')
  3. AnnotationURLCitation(end_index=1125, start_index=1001, title='The uteroglobin fold - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11193783/#:~:text=medium,the%20cap%20domain%20of%20Xanthobacter')
  4. AnnotationURLCitation(end_index=1394, start_index=1264, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=%2A%2027.Chowdhury%20B%2C%20Mantile,2%20%5BDOI')
  5. AnnotationURLCitation(end_index=1867, start_index=1735, title='Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/36450281/#:~:text=Club%20cell%20secretory%20protein%20,Recent%20studies')
  6. AnnotationURLCitation(end_index=2183, start_index=1995, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=SCGB%201A1%20is%20the%20prototypic,mechanism%20of%20reducing%20inflammation%20and')
  7. AnnotationURLCitation(end_index=2318, start_index=2184, title='Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15148333/#:~:text=Uteroglobin%20,and%20Th2%20cytokine%20gene%20expression')
  8. AnnotationURLCitation(end_index=2721, start_index=2589, title='Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/36450281/#:~:text=Club%20cell%20secretory%20protein%20,Recent%20studies')
  9. AnnotationURLCitation(end_index=3275, start_index=3143, title='Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/36450281/#:~:text=Club%20cell%20secretory%20protein%20,Recent%20studies')
  10. AnnotationURLCitation(end_index=3659, start_index=3525, title='Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15148333/#:~:text=Uteroglobin%20,and%20Th2%20cytokine%20gene%20expression')
  11. AnnotationURLCitation(end_index=4278, start_index=4123, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=SCGB%201A1%20has%20anti,27%5D.%20SCGB%201A1%20is')
  12. AnnotationURLCitation(end_index=4575, start_index=4445, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=%2A%2027.Chowdhury%20B%2C%20Mantile,2%20%5BDOI')
  13. AnnotationURLCitation(end_index=4940, start_index=4760, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=inactivation%20of%20PLA2%2C%20sequestration%20of,27%5D.%20SCGB%201A1%20is')
  14. AnnotationURLCitation(end_index=5327, start_index=5222, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=,PMC%20free%20article')
  15. AnnotationURLCitation(end_index=5729, start_index=5624, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=,PMC%20free%20article')
  16. AnnotationURLCitation(end_index=6003, start_index=5824, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=Rev.%20%282007%29%2028%3A707%E2%80%9325.%2010.1210%2Fer.2007,mediated%20expression%20of%20genes')
  17. AnnotationURLCitation(end_index=6480, start_index=6325, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=SCGB%201A1%20has%20anti,27%5D.%20SCGB%201A1%20is')
  18. AnnotationURLCitation(end_index=6728, start_index=6573, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=SCGB%201A1%20has%20anti,27%5D.%20SCGB%201A1%20is')
  19. AnnotationURLCitation(end_index=7081, start_index=6947, title='Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15148333/#:~:text=Uteroglobin%20,and%20Th2%20cytokine%20gene%20expression')
  20. AnnotationURLCitation(end_index=7237, start_index=7082, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=SCGB%201A1%20has%20anti,27%5D.%20SCGB%201A1%20is')
  21. AnnotationURLCitation(end_index=7590, start_index=7425, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=metabolites%2C%20and%20is%20considered%20a,SCGB%201A1%20is')
  22. AnnotationURLCitation(end_index=7913, start_index=7733, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=SCGB%201A1%20has%20anti,of%20neutrophil%20activating%20arachidonic%20acid')
  23. AnnotationURLCitation(end_index=8284, start_index=8153, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=prostaglandins%20,32%E2%80%9334%29%2C%20whereas')
  24. AnnotationURLCitation(end_index=8586, start_index=8455, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=prostaglandins%20,32%E2%80%9334%29%2C%20whereas')
  25. AnnotationURLCitation(end_index=9021, start_index=8883, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=%28including%20IL,cytokine%20surges%20in%20the%20lungs')
  26. AnnotationURLCitation(end_index=9555, start_index=9400, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=SCGB%201A1%20has%20anti,27%5D.%20SCGB%201A1%20is')
  27. AnnotationURLCitation(end_index=9687, start_index=9556, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=prostaglandins%20,32%E2%80%9334%29%2C%20whereas')
  28. AnnotationURLCitation(end_index=10233, start_index=10053, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=inactivation%20of%20PLA2%2C%20sequestration%20of,27%5D.%20SCGB%201A1%20is')
  29. AnnotationURLCitation(end_index=10668, start_index=10563, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=,PMC%20free%20article')
  30. AnnotationURLCitation(end_index=11190, start_index=11059, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=prostaglandins%20,32%E2%80%9334%29%2C%20whereas')
  31. AnnotationURLCitation(end_index=11329, start_index=11191, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=%28including%20IL,cytokine%20surges%20in%20the%20lungs')
  32. AnnotationURLCitation(end_index=11766, start_index=11635, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=,mediators%20of%20airway%20diseases%20including')
  33. AnnotationURLCitation(end_index=11929, start_index=11767, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=vitro%20experiments%20with%20AM%20culture,cytokine%20surges%20in%20the%20lungs')
  34. AnnotationURLCitation(end_index=12285, start_index=12154, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=,mediators%20of%20airway%20diseases%20including')
  35. AnnotationURLCitation(end_index=12601, start_index=12470, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=,mediators%20of%20airway%20diseases%20including')
  36. AnnotationURLCitation(end_index=12801, start_index=12706, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=,PLoS%20One')
  37. AnnotationURLCitation(end_index=14219, start_index=14085, title='Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15148333/#:~:text=Uteroglobin%20,and%20Th2%20cytokine%20gene%20expression')
  38. AnnotationURLCitation(end_index=14525, start_index=14387, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=%28including%20IL,cytokine%20surges%20in%20the%20lungs')
  39. AnnotationURLCitation(end_index=14706, start_index=14526, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=inactivation%20of%20PLA2%2C%20sequestration%20of,27%5D.%20SCGB%201A1%20is')
  40. AnnotationURLCitation(end_index=15039, start_index=14876, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=inflammatory%20responses%20in%20the%20absence,39%E2%80%9341%29%3B%20respiratory')
  41. AnnotationURLCitation(end_index=15217, start_index=15040, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=match%20at%20L208%20myelopoiesis%20and%2For,status%20associated%20with%20Scgb1a1%20deficiency')
  42. AnnotationURLCitation(end_index=15688, start_index=15578, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=,33')
  43. AnnotationURLCitation(end_index=15832, start_index=15689, title='Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/36450281/#:~:text=blood%20and%20urine,therapeutic%20modality%20in%20lung%20disease')
  44. AnnotationURLCitation(end_index=16122, start_index=16012, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=,33')
  45. AnnotationURLCitation(end_index=16594, start_index=16451, title='Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/36450281/#:~:text=blood%20and%20urine,therapeutic%20modality%20in%20lung%20disease')
  46. AnnotationURLCitation(end_index=17001, start_index=16877, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=37,View%20Article')
  47. AnnotationURLCitation(end_index=17560, start_index=17419, title='The safety, pharmacokinetics, and anti-inflammatory effects of intratracheal recombinant human Clara cell protein in premature infants with respiratory distress syndrome - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15774846/#:~:text=The%20safety%2C%20pharmacokinetics%2C%20and%20anti,Recombinant')
  48. AnnotationURLCitation(end_index=18055, start_index=17895, title='Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/36450281/#:~:text=CCSP%20levels%2C%20thought%20to%20be,therapeutic%20modality%20in%20lung%20disease')
  49. AnnotationURLCitation(end_index=18463, start_index=18366, title='SCGB1A1 [Human] | GeneGlobe', type='url_citation', url='https://geneglobe.qiagen.com/us/knowledge/gene/ENSG00000149021#:~:text=')
  50. AnnotationURLCitation(end_index=19164, start_index=19009, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=SCGB%201A1%20has%20anti,27%5D.%20SCGB%201A1%20is')
  51. AnnotationURLCitation(end_index=19296, start_index=19165, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=prostaglandins%20,32%E2%80%9334%29%2C%20whereas')
  52. AnnotationURLCitation(end_index=19734, start_index=19602, title='Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/36450281/#:~:text=Club%20cell%20secretory%20protein%20,Recent%20studies')
  53. AnnotationURLCitation(end_index=19915, start_index=19735, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=inactivation%20of%20PLA2%2C%20sequestration%20of,27%5D.%20SCGB%201A1%20is')
  54. AnnotationURLCitation(end_index=20330, start_index=20185, title='The Club Cell Marker SCGB1A1 Downstream of FOXA2 is Reduced in Asthma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6543749/#:~:text=The%20Club%20Cell%20Marker%20SCGB1A1,Clara%20cell%20secretory')
  55. AnnotationURLCitation(end_index=20481, start_index=20331, title='An update in club cell biology and its potential relevance to chronic obstructive pulmonary disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10110710/#:~:text=An%20update%20in%20club%20cell,%E2%9C%89%7D%2C%20Ngan%20Fung%20Li')
  56. AnnotationURLCitation(end_index=20924, start_index=20769, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=SCGB%201A1%20has%20anti,27%5D.%20SCGB%201A1%20is')
  57. AnnotationURLCitation(end_index=21063, start_index=20925, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=%28including%20IL,cytokine%20surges%20in%20the%20lungs')
  58. AnnotationURLCitation(end_index=21604, start_index=21444, title='Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/36450281/#:~:text=CCSP%20levels%2C%20thought%20to%20be,therapeutic%20modality%20in%20lung%20disease')
  59. AnnotationURLCitation(end_index=21990, start_index=21856, title='Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15148333/#:~:text=Uteroglobin%20,and%20Th2%20cytokine%20gene%20expression')
  60. AnnotationURLCitation(end_index=22171, start_index=21991, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=inactivation%20of%20PLA2%2C%20sequestration%20of,27%5D.%20SCGB%201A1%20is')
  61. AnnotationURLCitation(end_index=22547, start_index=22392, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=SCGB%201A1%20has%20anti,27%5D.%20SCGB%201A1%20is')
  62. AnnotationURLCitation(end_index=22713, start_index=22548, title='Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation | PLOS One', type='url_citation', url='https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096217#:~:text=metabolites%2C%20and%20is%20considered%20a,SCGB%201A1%20is')
  63. AnnotationURLCitation(end_index=23031, start_index=22893, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=%28including%20IL,cytokine%20surges%20in%20the%20lungs')
  64. AnnotationURLCitation(end_index=23163, start_index=23032, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=,mediators%20of%20airway%20diseases%20including')
  65. AnnotationURLCitation(end_index=23475, start_index=23370, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=,PMC%20free%20article')
  66. AnnotationURLCitation(end_index=23823, start_index=23693, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=%2A%2027.Chowdhury%20B%2C%20Mantile,2%20%5BDOI')
  67. AnnotationURLCitation(end_index=24134, start_index=24039, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=,PLoS%20One')
  68. AnnotationURLCitation(end_index=24448, start_index=24316, title='Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/36450281/#:~:text=Club%20cell%20secretory%20protein%20,Recent%20studies')
  69. AnnotationURLCitation(end_index=24609, start_index=24449, title='Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/36450281/#:~:text=CCSP%20levels%2C%20thought%20to%20be,therapeutic%20modality%20in%20lung%20disease')
  70. AnnotationURLCitation(end_index=24865, start_index=24752, title='The cytokine-driven regulation of secretoglobins in normal human upper airway and their expression, particularly that of uteroglobin-related protein 1, in chronic rhinosinusitis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3063214/#:~:text=Secretoglobin%20,Clara%20cell')
  71. AnnotationURLCitation(end_index=25147, start_index=25013, title='Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15148333/#:~:text=Uteroglobin%20,and%20Th2%20cytokine%20gene%20expression')
  72. AnnotationURLCitation(end_index=25430, start_index=25306, title='The uteroglobin fold - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11193783/#:~:text=medium,the%20cap%20domain%20of%20Xanthobacter')
  73. AnnotationURLCitation(end_index=25725, start_index=25587, title='Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7558713/#:~:text=%28including%20IL,cytokine%20surges%20in%20the%20lungs')