Annexin I and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytes
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 A2 (PLA2) and cyclooxygenase (COX) activities and prostagl...
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| Format: | Article |
| Language: | English |
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Wiley
2000-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1080/09629350020018357 |
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| author | Annaleise V. Sampey Paul Hutchinson Eric F. Morand |
| author_facet | Annaleise V. Sampey Paul Hutchinson Eric F. Morand |
| author_sort | Annaleise V. Sampey |
| collection | DOAJ |
| description | 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 A2 (PLA2) and cyclooxygenase (COX) activities and
prostaglandin E2 (PGE2) release in cultured human fibroblast-like synoviocytes (FLS). Annexin I binding sites on human osteoarthritic (OA) FLS were detected by ligand binding flow cytometry. PLA2 activity was measured using 3H-arachidonic acid release, PGE2 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 PLA2 activity, which was reversed by IL-1β. In contrast, DEX inhibited IL-1β-induced PLA2 activity but not constitutive activity. DEX but not annexin I peptide inhibited IL-1β-induced PGE2 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 PLA2 and COX by annexin I and DEX support the hypothesis that COX is rate-limiting for PGE2 synthesis in FLS. The effect of annexin I but not DEX on constitutive PLA2 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 PGE2 production suggests PGE2-independent mechanisms for the anti-inflammatory effects of annexin I in vivo. |
| format | Article |
| id | doaj-art-81ffe973ad734c7c80b72ed46ba7dd0e |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2000-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-81ffe973ad734c7c80b72ed46ba7dd0e2025-02-03T05:53:50ZengWileyMediators of Inflammation0962-93511466-18612000-01-0193-412513210.1080/09629350020018357Annexin I and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytesAnnaleise V. Sampey0Paul Hutchinson1Eric F. Morand2Monash Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Melbourne, AustraliaMonash Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Melbourne, AustraliaMonash Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Melbourne, AustraliaAnnexin 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 A2 (PLA2) and cyclooxygenase (COX) activities and prostaglandin E2 (PGE2) release in cultured human fibroblast-like synoviocytes (FLS). Annexin I binding sites on human osteoarthritic (OA) FLS were detected by ligand binding flow cytometry. PLA2 activity was measured using 3H-arachidonic acid release, PGE2 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 PLA2 activity, which was reversed by IL-1β. In contrast, DEX inhibited IL-1β-induced PLA2 activity but not constitutive activity. DEX but not annexin I peptide inhibited IL-1β-induced PGE2 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 PLA2 and COX by annexin I and DEX support the hypothesis that COX is rate-limiting for PGE2 synthesis in FLS. The effect of annexin I but not DEX on constitutive PLA2 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 PGE2 production suggests PGE2-independent mechanisms for the anti-inflammatory effects of annexin I in vivo.http://dx.doi.org/10.1080/09629350020018357 |
| spellingShingle | Annaleise V. Sampey Paul Hutchinson Eric F. Morand Annexin I and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytes Mediators of Inflammation |
| title | Annexin I and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytes |
| title_full | Annexin I and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytes |
| title_fullStr | Annexin I and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytes |
| title_full_unstemmed | Annexin I and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytes |
| title_short | Annexin I and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytes |
| title_sort | annexin i and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytes |
| url | http://dx.doi.org/10.1080/09629350020018357 |
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