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Am J Physiol Gastrointest Liver Physiol 282: G981-G990, 2002. First published January 9, 2002; doi:10.1152/ajpgi.00293.2001
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Vol. 282, Issue 6, G981-G990, June 2002

IL-10 receptor and coreceptor expression in quiescent and activated hepatic stellate cells

Philippe Mathurin1, Shigang Xiong1, Kusum K. Kharbanda4, Nary Veal1, Takeo Miyahara1, Kenta Motomura1, Richard A. Rippe5, Max G. Bachem6, and Hidekazu Tsukamoto1,2,3

Departments of 1 Pathology and 2 Medicine, Keck School of Medicine of the University of Southern California, Los Angeles 90089; 3 Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda, California 91343; 4 Department of Veterans Affairs Medical Center, Omaha, Nebraska 68198; 5 Department of Medicine, University of North Carolina at Chapel Hill, North Carolina 27599-7038; and 6 Institute for Clinical Chemistry, University of Ulm, Ulm, Germany 89070

Interleukin (IL)-10 expression is induced in activated hepatic stellate cells (HSC) in vitro and in vivo. We analyzed expression of IL-10 receptor (IL-10R) and coreceptor cytokine receptor family (CRF2-4) in HSC. We aimed to clone and sequence partial cDNA for rat IL-10R and CRF2-4, determine their expression in activated rat HSC in vivo and in vitro, and examine the biological responsiveness of HSC to exogenous IL-10. PCR cloning and sequencing of partial rat IL-10R and CRF2-4 cDNAs revealed 86% homology with corresponding mouse sequences. In hepatic macrophages, Northern blot with cloned IL-10R cDNA detected an expected 3.5-kb transcript, and IL-10R and CRF2-4 mRNAs showed steady constitutive expression after in vitro lipopolysaccharide treatment or cholestatic liver injury. IL-10R mRNA expression, as confirmed by immunohistochemistry, was induced 20.1- and 8.6-fold in HSC from cholestatic livers and 7-day culture-activated HSC, respectively but CRF2-4 mRNA levels were unchanged. Under serum-free conditions, IL-10 had minimal effects on collagen production but reduced DNA synthesis, matrix metalloprotease-2 mRNA levels, and activity in HSC. With serum, IL-10 inhibited both collagen production and DNA synthesis but had no effect on procollagen-alpha 1(I) mRNA levels. This shows concomitant induction of IL-10R but not CRF2-4 to that of IL-10 by activated HSC in vitro and in vivo and associated acquisition of the responsiveness to IL-10, entailing complex effects on HSC.

interleukin-10; cytokine receptor family 2-4; procollagen-alpha 1(I) ; matrix metalloprotease-2; matrix metalloprotease-13; monocyte-chemoattracting protein-1; liver fibrosis


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