Suppressive effect of antiflammin-2 on compound 48/80-induced conjunctivitis. Role of phospholipase A2s and inducible nitric oxide synthase.
Phospholipase A2s (PLA2s) are a family of esterases that initiate the arachidonic acid cascade, which results in the production of numerous inflammatory mediators. We investigated the expression of Group I and II PLA2 proteins and Group II mRNA in normal conjunctivae and in the conjunctivae of mice with compound 48/80-induced conjunctivitis. Conjunctivitis was induced in C57BL/6 mice by topical instillation of compound 48/80 (C48/80). Mice were then treated with corticosteroid (Pred Forte), antiflammin-2 (AF2, a synthetic peptide that inhibits PLA2), or a placebo (Dacriose, an isotonic, buffered, sterile eye irrigating solution). Low levels of PLA2s were detected on the epithelium of normal conjunctivae. One hr after C48/80 instillation, the expression of PLA2s appeared and increased in the substantia propria, peaked at 6 hr, and returned to baseline 72 hr later. Compared to the placebo, the conjunctivitis was moderate in the AF2-treated group and mild in Pred Forte-treated group. The expression of PLA2s was suppressed in mice treated with Pred Forte and AF2. iNOS mRNA was also diminished in the AF2- and Pred Forte-treated groups. The mechanisms by which anti-allergic medications suppress conjunctivitis may involve the inhibition of PLA2s and iNOS.
Section on Immunopathology, National Eye Institute, National Institute of Health, Bethesda, MD, USA.
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D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003228:Conjunctiva / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D015342:DNA Probes / Q000737:chemistry; D005260:Female; D005938:Glucocorticoids; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009842:Oligopeptides / Q000494:pharmacology*; D009883:Ophthalmic Solutions; D010446:Peptide Fragments / Q000494:pharmacology*; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D011239:Prednisolone / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015342:DNA Probes; D005938:Glucocorticoids; D009842:Oligopeptides; D009883:Ophthalmic Solutions; D010446:Peptide Fragments; D012333:RNA, Messenger; C064647:antiflammin P2; D003189:p-Methoxy-N-methylphenethylamine; C009935:prednisolone acetate; D011239:Prednisolone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D010741:Phospholipases A; D054467:Phospholipases A2