Research On The Regulation Of Inflammatory Signal Pathway By Resistin

Resistin is a 114-amino-acid polypeptide which belongs to resistin-like molecule (RELM) family characterized by a highly conserved cysteine-rich C terminus. Recently, resistin has emerged as a novel pro-inflammatory factor. The association between resistin and inflammation has also been demonstrated in rheumatoid arthritis and other diseases, where resistin is capable of inducing vascular adhesion molecule expression and promoting leukocyte infiltration into tissues.Two cyclooxygenease, COX-1 and COX-2, have been identified as the key enzymes regulating the production of prostaglandins. COX-2 is an inflammation-induced enzyme that remains undetectable in most mammalian tissues under basal conditions and is highly activated at the sites of inflammation. Some important pro-inflammatory cytokines, such as TNF-alpha, can also upregulate COX-2 expression via NF-kappa B pathway.In this study, by choosing the important cytokine resistin and using real-time PCR, transfection and western blotting, we studied the regulation effect of COX-2 by resistin, and also researched the anti-inflammatory effect of chemerin-15 and got the following results:1. Compared with controls, resistin remarkably upregulated COX-2 expression in RAW264.7 macrophage cells. Administration of anti-resistin antibody could reverse this effect.2. Induction of COX-2 by resistin was markedly reduced in the presence of either dominant negative mutant IκBαor PDTC, a pharmacological inhibitor of NF-κB. NF-κB subunit p65 was also upregulated by resistin.3. Moreover, we found that transforming growth factor-β-activated kinase 1 (TAK1), a mitogen-activated protein kinase kinase kinase (MAPKKK), could be activated in response to resistin. 4. Stimulated RAW cells with LPS, resistin and C15, measured the expression of COX-2 and iNOS. The results indicated that the inducing of COX-2 and iNOS could markedly reduced by C15.5. We used macrophages as a model, using LPS as a proinflammatory substance representation measured the translocation of NF-κB subunit p65. The results indicated that the ranslocation of p65 induced by LPS could be obviously inhibited by C15. This result also proved the pecific mechanism of C15 generating antiinflammation.