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D. Chen, S. Epstein, J. M. Wolosin, P. A. Asbell; SPLA2-IIa Stimulates Inflammatory Cytokine Production in Human Ocular Surface Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2402.
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Secretory phospholipaseA2-IIa (sPLA2-IIa) is constitutivelyexpressed at high levels in tears where it has been demonstratedto exert a powerful bactericidal effect. Yet in multiple otherconditions, most notably rheumatoid arthritis and septic shock,this enzyme has been proven to be an important inflammatorymediator. The inflammatory mediator effect of sPLA2-IIa in tearhas not been explored. Our previous studies have showed thatsPLA2 significantly stimulates increased PGE2 production onChang's conjunctival cells and murine conjunctival organ culture,and has showed synergistic effect with pre-inflammatory cytokineTNFa. In the current study we further explored the inflammatory-mediatingeffects of secretory sPLA2-IIa on ocular surface cells by detectingthe production of inflammatory cytokines with a cRNA array analysis.
Chang's human conjunctival epithelial cells were seeded in 24well plate and treated with hsPLA2-IIa, with or without TNFa.After 24 hours, the cells were harvested and RNA isolated, inflammatorycytokine/chemokine production was detected by a Pathway-FocusedMicroarray (SuperArray) assay.
sPLA2 alone stimulated inflammatory cytokine productions (CCL5,IL-1b and IL-6), similar to low concentration of TNFa. Combineduse of sPLA2 and TNFa resulted in a synergistic effect on productionsof CCL5 and CCL25.
These findings, together with our previous data on PGE2 production,suggests that sPLA2-IIa may be an important inflammatory mediatorin the ocular surface, especially in conditions where the cellsurface is compromised. Further examination of the role of theseabundant enzyme on chronic inflammation is warranted.
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