title: Adiponectin induces CCL20 expression synergistically with IL-6 and TNF-α in THP-1 macrophages.
abstract: 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 24h with Ad, IL-6, or TNF-α 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-α 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-α 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-α 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-α. In conclusion, gAd played an important role in CCL20 expression, and MMP-12 induced by IL-6 or TNF-α was involved in the synergistic effect of fAd and cytokines.
authors.affiliation: Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan. suzuki.miho@chugai-pharm.co.jp
authors.forename: Miho
authors.initials: M
authors.lastname: Suzuki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mihara
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D002208:Caproates / Q000494:pharmacology; D002460:Cell Line; D054418:Chemokine CCL20 / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D011083:Polycyclic Compounds; D060888:Real-Time Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C476600:3-(((2,2-dimethyl-1-(((2-methoxy-1-phenylethyl)amino)carbonyl)propyl)amino)carbonyl)-6-(3-methyl-4-phenylphenyl)hexanoic acid; D052242:Adiponectin; C108355:CCL20 protein, human; D002208:Caproates; D054418:Chemokine CCL20; D015850:Interleukin-6; D011083:Polycyclic Compounds; D014409:Tumor Necrosis Factor-alpha; D053508:Matrix Metalloproteinase 12; D014633:Valine; D013755:Tetradecanoylphorbol Acetate