sPLA2-IIa is an inflammatory mediator when the ocular surface is compromised.
sPLA2-IIa is an enzyme at high concentration in tears that has been known as an innate barrier of the ocular surface against microbial infection. sPLA2-IIa and other enzymes in the same protein family are known to hydrolyze fatty acids resulting in the generation of free arachidonic acid (AA) and lysophospholipids, which are the precursors of pro-inflammatory lipid mediators, such as PGE(2). sPLA2-IIa has been shown to be an inflammatory mediator in non-ocular inflammatory diseases such as rheumatoid arthritis (RA). It was also found to be increased in the tears of the patients with dry eye disease, chronic blepharitis and contact lens intolerance. However, the role of sPLA2-IIa in chronic ocular surface inflammation has yet to be determined. In the current study, we examined the potential role of sPLA2-IIa in inflammation of ocular surface diseases. Our results show that the activity of sPLA2-IIa was significantly increased in tears from dry eye disease patients compared with that from normal subjects. Also, sPLA2-IIa stimulated the production of PGE(2) in ocular surface epithelial cell cultures. The stimulating effect was markedly enhanced when the cells or tissues were pre-compromised with TNF-alpha, IL-1beta or desiccation. Furthermore, sPLA2-IIa stimulated inflammatory cytokine production in the ocular surface epithelial cell cultures in vitro. To our knowledge, this is the first report regarding the role of sPLA2-IIa as an inflammatory mediator in ocular surface inflammation. These findings indicate that sPLA2-IIa may play an important role in chronic ocular surface inflammation, especially when the ocular surface is compromised.
Chen
Dongmei
D
Department of Ophthalmology, The Mount Sinai School of Medicine, New York, NY 10029, USA.
Wei
Yi
Y
Li
Xiaohong
X
Epstein
Seth
S
Wolosin
J Mario
JM
Asbell
Penny
P
D000328:Adult; D000368:Aged; D000818:Animals; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015352:Dry Eye Syndromes / Q000201:enzymology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D054501:Group II Phospholipases A2 / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009924:Organ Culture Techniques; D013539:Simian virus 40; D013666:Tears / Q000201:enzymology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D054501:Group II Phospholipases A2; D015232:Dinoprostone