Visfatin contributes to the differentiation of monocytes into macrophages through the differential regulation of inflammatory cytokines in THP-1 cells

초록

Visfatin is a novel multifunctional adipocytokine with inflammatory properties. Although a link between visfatin and atherosclerosis has recently been suggested, its actions in the development of atherosclerosis remain unknown. Therefore, we investigated a potential role and underlying mechanism(s) of visfatin in monocytes/macrophages differentiation, a critical early step in atherogenesis, using phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cell models. The co-incubation of PMA with visfatin-induced CD36 expression with a concomitant increase in the phagocytosis of latex beads compared with PMA alone treatment. Moreover, visfatin markedly increased interleukin (IL)-1 beta secretion by enhancing IL-1 beta mRNA stability in a short-term incubation. Visfatin also significantly elevated the secretion of IL-6 as well as IL-1 beta in a longer incubation period, which was partially suppressed by nuclear factor-kappa B (NF-kappa B) inhibitor, BAY11-7082, and c-Jun-N-terminal kinase (JNK) inhibitor, SP600125. Furthermore, silencing IL-1 beta successfully blocked IL-6 secretion, CD36 expression, and NF-kappa B activation in response to visfatin. Collectively, these results suggest that visfatin enhances the IL-1 beta-dependent induction of IL-6 and CD36 via distinct signaling pathways mediated by JNK and NF-kappa B, respectively, and consequently, leading to the acceleration of monocytes/macrophages differentiation. (C) 2014 Elsevier Inc. All rights reserved.

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