IL-6 downregulates transcription of NTPDase2 via specific promoter elements.

American Journal of Physiology. Gastrointestinal and Liver Physiology
Jin YuJonathan A Dranoff

Abstract

Bile ductular proliferation is markedly upregulated in biliary fibrosis and cirrhosis. However, the mechanisms regulating this upregulation in bile ductular proliferation have not been defined. Recently, we demonstrated that expression of the ectonucleotidase nucleoside triphosphate diphosphohydrolase-2 (NTPDase2/Entpd2) by portal fibroblasts (PF) is a critical regulator of bile ductular proliferation. Since interleukin 6 (IL-6) is markedly upregulated in biliary cirrhosis, our aims were to determine the role and mechanism of IL-6 in the regulation of NTPDase2 by PF. We found that IL-6 downregulated NTPDase2 protein expression in a concentration-dependent and time-dependent fashion but did not alter PF alpha-smooth muscle actin expression. IL-6 markedly downregulated NTPDase2 mRNA expression. Expression of the IL-6 receptor gp130 but not the IL-6 receptor gp80 was detected in PF. Two transcription start sites were identified in rat Entpd2 by the method of RNA ligase-mediated rapid amplification of 5' cDNA ends. The minimal promoter construct, but not shorter constructs, was downregulated by IL-6. Three putative IL-6 response elements were identified in silico and mutated. Mutation of all three response elements, but not fewer e...Continue Reading

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Citations

Aug 18, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Michel FaustherJonathan A Dranoff
Sep 11, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Gaurav SyalJonathan A Dranoff
Jan 13, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jin YuJonathan A Dranoff
Mar 9, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jonathan A Dranoff, Rebecca G Wells
Dec 17, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Michel Fausther, Jonathan A Dranoff
Oct 26, 2016·Differentiation; Research in Biological Diversity·Daniel KarinTatiana Kisseleva
Nov 22, 2014·Physiological Reports·DaShawn A HickmanJonathan A Dranoff

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