Adiponectin induces CCL20 expression synergistically with IL-6 and TNF-α in THP-1 macrophages

Adiponectin (Ad) is an adipokine secreted from adipocytes. It is reported that Ad has many biological activities. However, its influence on inflammation is controversial. In the present study, we examined the influence of Ad on production of CCL20 from THP-1 macrophages. THP-1 macrophages were prepared from THP-1 monocytes by PMA treatment. THP-1 macrophages were cultured for 24 h with Ad, IL-6, or TNF-alpha alone or with combinations of Ad and cytokines. CCL20 mRNA expression was then determined by real-time PCR. Full-length Ad (fAd) slightly but significantly induced CCL20 mRNA expression, and interestingly, co-stimulation with fAd and IL-6 or with fAd and TNF-alpha synergistically increased the expression of CCL20 mRNA. We explored the mechanism behind the synergistic effect of fAd and these cytokines. fAd did not affect the expression of receptors for IL-6 and TNF, and IL-6 and TNF-alpha did not increase the expression of the receptor for Ad in THP-1 macrophages. The increased expression of CCL20 by fAd is much higher in THP-1 macrophages compared with THP-1 monocytes. Furthermore, MMP-12 production was increased by IL-6 and TNF-alpha in THP-1 macrophages but it was not detectable in THP-1 monocytes. Treatment of fAd with MMP-12 induced globular Ad (gAd), and the expression of CCL20 in THP-1 macrophages was increased more potently by gAd than by fAd. MMP inhibitor (UK370106) inhibited the expression of CCL20 induced by co-stimulation with fAd and IL-6 or TNF-alpha. In conclusion, gAd played an important role in CCL20 expression, and MMP-12 induced by IL-6 or TNF-alpha was involved in the synergistic effect of fAd and cytokines. (C) 2012 Elsevier Ltd. All rights reserved.