AIM:To investigate the mechanisms involved in a possible modulator role of interleukin(IL) -6 signalling on CYR61-CTGF-NOV(CCN) 2/connective tissue growth factor(CTGF) expression in hepatocytes(PC) and to look for a relation between serum concentrations of these two parameters in patients with acute inflammation. METHODS:Expression of CCN2/CTGF,p-STAT3,p-Smad 3/1 and p-Smad2 was examined in primary freshly isolated rat or cryo-preserved human PC exposed to various stimuli by Western blotting,electrophoretic mobility shift assay(EMSA) ,reporter-gene-assays and reversetranscriptase polymerase chain reaction. RESULTS:IL-6 strongly down-regulated CCN2/CTGF protein and mRNA expression in PC,enhanceable by extracellular presence of the soluble IL-6 receptor gp80,and supported by an inverse relation between IL-6 and CCN2/CTGF concentrations in patients’sera.The inhi-bition of TGFβ1 driven CCN2/CTGF expression by IL-6 did not involve a modulation of Smad2(and Smad1/3) signalling.However,the STAT3 SH2 domain binding peptide,a selective inhibitor of STAT3 DNA binding activity,counteracted the inhibitory effect of IL-6 on CCN2/CTGF expression much more pronounced than pyrrolidine-dithiocarbamate,an inhibitor primarily of STAT3 phosphorylation.An EMSA confirmed STAT3 binding to the proposed proximal STAT binding site in the CCN2/CTGF promoter. CONCLUSION:CCN2/CTGF is identified as a hepatocellular negative acute phase protein which is downregulated by IL-6 via the STAT3 pathway through interaction on the DNA binding level. AIM: To investigate the mechanisms involved in a possible modulator role of interleukin (IL) -6 signaling on CYR61-CTGF-NOV (CCN) 2 / connective tissue growth factor (CTGF) expression in hepatocytes (PC) and to look for a relation METHODS of Expression of CCN2 / CTGF, p-STAT3, p-Smad 3/1 and p-Smad2 was examined in primary freshly isolated rat or cryo-preserved human PC exposed to various stimuli by Western blotting, electrophoretic mobility shift assay (EMSA), reporter-gene-assays and reversetranscriptase polymerase chain reaction. RESULTS: IL-6 strongly down-regulated CCN2 / CTGF protein and mRNA expression in PC, enhance by extracellular presence of the soluble IL-6 receptor gp80, and supported by an inverse relation between IL-6 and CCN2 / CTGF concentrations in patients’sera. inhi-bition of TGFβ1 driven CCN2 / CTGF expression by IL-6 did not involve a modulation of Smad2 and Smad1 / 3) signalling.However, the S TAT3 SH2 domain binding peptide, a selective inhibitor of STAT3 DNA binding activity, counteracted the inhibitory effect of IL-6 on CCN2 / CTGF expression much much pronounced than pyrrolidine-dithiocarbamate, an inhibitor of STAT3 phosphorylation. An EMSA confirmed STAT3 binding to the It is proposed that the proximal STAT binding site in the CCN2 / CTGF promoter. CONCLUSION: CCN2 / CTGF is identified as a hepatocellular negative acute phase protein which is downregulated by IL-6 via the STAT3 pathway through interaction on the DNA binding level.