Adiponectin reduces C-reactive protein expression and downregulates STAT3 phosphorylation induced by IL-6 in HepG2 cells.
By playing a direct proatherogenic role, C-reactive protein (CRP) is a potent independent predictor of future cardiovascular events. CRP is predominately synthesized by hepatocytes when stimulated by interleukin-6 (IL-6). In response to IL-6, the signal transducer and activator of transcription 3 (STAT3) becomes phosphorylated on tyrosine and serine residues. Phosphorylated STAT3 then activates CRP gene transcription. In obesity-related disorders such as diabetes, metabolic syndrome, and cardiovascular diseases, the circulating levels of CRP and adiponectin are inversely correlated, suggesting that these two factors might reciprocally regulate each other. We investigated the possibility that adiponectin inhibits CRP production in HepG(2) cells elicited by IL-6. CRP gene expression was determined using ELISA and semi-quantitative RT-PCR, and the phosphorylation of STAT3 was investigated with western blot. Adiponectin reduced IL-6-induced CRP mRNA levels in HepG(2) cells and CRP protein secretion. Preincubating HepG(2) cells with adiponectin led to a decline in STAT3 phosphorylation on both tyrosine and serine residues. Our results demonstrated that adiponectin suppresses CRP synthesis and secretion from HepG(2) cells and suggested that the suppression may be mediated through inhibition of the STAT3 pathway. The finding provides a novel insight into the molecular linkage between obesity and vascular diseases.
Sun
Haiyun
H
Department of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang Dirstrict, 150086, Harbin, Heilongjiang Province, People's Republic of China.
Zhang
Yingnan
Y
Gao
Ping
P
Li
Qiang
Q
Sun
Yuqian
Y
Zhang
Jinchao
J
Xu
Changqing
C
D052242:Adiponectin / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D052242:Adiponectin; D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D002097:C-Reactive Protein