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- Title
Annexin I and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytes.
- Authors
Sampey, Annaleise V.; Hutchinson, Paul; Morand, Eric F.
- Abstract
Annexin I is a glucocorticoid-induced mediator with anti-inflammatory activity in animal models of arthritis. We studied the effects of a bioactive annexin I peptide, ac 2-26, dexamethasone (DEX), and interleukin-1β (IL-1β) on phospholipase A[sub 2] (PLA[sub 2]) and cyclooxygenase (COX) activities and prostaglandin E[sub 2] (PGE[sub 2]) release in cultured human fibroblast-like synoviocytes (FLS). Annexin I binding sites on human osteoarthritic (OA) FLS were detected by ligand binding flow cytometry. PLA[sub 2] activity was measured using [sup 3]H-arachidonic acid release, PGE[sub 2] release and COX activity by ELISA, and COX2 content by flow cytometry. Annexin I binding sites were present on human OA FLS. Annexin I peptide ac 2-26 exerted a significant concentration-dependent inhibition of FLS constitutive PLA activity, which was reversed by IL-1β. In contrast, DEX inhibited IL-1β-induced PLA[sub 2] activity but not constitutive activity. DEX but not annexin I peptide inhibited IL-1β-induced PGE[sub 2] release. COX activity and COX2 expression were significantly increased by IL-1β. Annexin I peptide demonstrated no inhibition of constitutive or IL-1β-induced COX activity. DEX exerted a concentration-dependent inhibition of IL-1β-induced but not constitutive COX activity. Uncoupling of inhibition of PLA[sub 2] and COX by annexin I and DEX support the hypothesis that COX is rate-limiting for PGE[sub 2] synthesis in FLS. The effect of annexin I but not DEX on constitutive PLA[sub 2] activity suggests a glucocorticoid-independent role for annexin I in autoregulation of arachidonic acid production. The lack of effect of annexin I on cytokine-induced PGE[sub 2] production suggests PGE[sub 2]-independent mechanisms for the anti-inflammatory effects of annexin I in vivo.
- Subjects
BIOACTIVE compounds; ANNEXINS; PHOSPHOLIPASES; CYCLOOXYGENASES; PROSTAGLANDINS
- Publication
Mediators of Inflammation, 2000, Vol 9, Issue 3/4, p125
- ISSN
0962-9351
- Publication type
Article
- DOI
10.1080/09629350020018357