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Interleukin-1 receptor antagonist intervenes in signaling between different types of synoviocytes in rats with adjuvant arthritis

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Aim: To investigate the mechanisms of interleukin-1 receptor antagonist (IL-1ra) in the treatment of adjuvant arthritis (AA). Methods: AA was induced in rats by treatment with Freund's complete adjuvant (FCA). Rats were given an intracutaneous injection of IL-1ra (2.5,10,40 mg/kg, 3 times per day) from d 14 to d 21 after immunization. Synoviocyte proliferation and the activity of IL-1 were determined by using MTT assay. Tumor necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) concentrations were measured by radioimmunoassay. The ultrastructure of synoviocytes was observed by using a transmission electron microscope. Phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulating kinase (ERK) and p38 kinase were detected by Western blot analysis. Results: IL-1ra (10 and 40 mg/kg, ic, d 14-21) modulated the secondary inflammatory reaction (P<0.01), ultrastructure of synoviocytes and mitogen-activated protein kinase (MAPK) phosphorylation in AA rats. The administration of IL-1ra (10 and 40 mg/kg, ic, d 14-21) in AA rats significantly decreased the production of IL-1, PGE2 and TNF-α by macrophage-like synoviocytes (MLS) (P<0.01). IL-1ra (2.5 mg/kg) also decreased the production of PGE2 (P<0.01) and TNF-α (P<0.05) by MLS in AA rats. The increased phosphorylation of MAPK and cell proliferation in fibro-blast-like synoviocytes (FLS) stimulated by supernatants of MLS in AA rats was also inhibited by IL-1ra (10 and 40 mg/kg, ic, d 14-21). Conclusion: IL-1ra has anti-inflammatory effects because it modulates the ultrastructure of synoviocytes, decreases the production of pro-inflammatory mediators by MLS, and inhibits the phosphorylation of MAPK in FLS.

Keywords: experimental arthritis; interleukin-1 receptor; mitogen-activated protein kinase; synovial membrane

Document Type: Research Article


Affiliations: 1: Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China 2: Key Laboratory of Anti-inflammation and Immunopharmacology in Anhui Province, Hefei 230032, China

Publication date: January 1, 2006


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