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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 bytreatment with Freund’s complete adjuvant (FCA).Rats were given an intracuta-neous injection of IL-1ra (2.5,10,40mg/kg,3 times per day) from d 14 to d 21 afterimmunization.Synoviocyte proliferation and the activity of IL-1 were determinedby using MTT assay.Tumor necrosis factor alpha (TNF-α) and prostaglandin E_2(PGE_2) concentrations were measured by radioimmunoassay.The ultrastructureof 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 (10and 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 40mg/kg,ic,d 14-21) in AA rats significantly decreased the production of IL-1,PGE_2and TNF-α by macrophage-like synoviocytes (MLS) (P<0.01).IL-1ra (2.5 mg/kg)also decreased the production of PGE_2(P<0.01) and TNF-α(P<0.05) by MLS inAA rats.The increased phosphorylation of MAPK and cell proliferation in fibro-blast-like synoviocytes (FLS) stimulated by supernatants of MLS in AA rats wasalso inhibited by IL-1ra (10 and 40 mg/kg,ic.d 14-21).Conclusion:IL-1ra hasanti-inflammatory effects because it modulates the ultrastructure of synoviocytes,decreases the production of pro-inflammatory mediators by MLS,and inhibits thephosphorylation of MAPK in FLS.
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 intracuta-neous injection of IL-1ra (2.5, 10, 40 mg / kg, 3 times per day) from d 14 to d 21 afterimmunization. Synoviocyte proliferation and the activity of IL-1 were determined by using MTT assay. Tumor necrosis factor alpha ) and prostaglandin E_2 (PGE_2) 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 Ultrastructure of synoviocytes and mitogen-activated protein kinase (MAPK) phosphorylation in AA rats (P <0.01), Western blot analysis.Results: IL-1ra (10 and 40 mg / kg, The administration of IL-1ra (10 and 40 mg / k IL-1ra (2.5 mg / kg) was also decreased (P <0.01) in AA rats significantly decreased the production of IL-1, PGE_2 and TNF-α by macrophage-like synoviocytes the production of PGE_2 (P <0.01) and TNF-α (P <0.05) by MLS inAA rats. increased phosphorylation of MAPK and cell proliferation in fibro-blast-like synoviocytes (FLS) stimulated by supernatants of MLS in AA rats wasalso inhibited by IL-1ra (10 and 40 mg / kg, ic.d 14-21) .Conclusion: IL-1ra hasanti-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.