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Articles in PresS, published online ahead of print January 9, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00293.2001
Submitted on July 10, 2001
Accepted on December 23, 2001
1 Pathology, University of Southern California, Los Angeles, CA, USA
2 Department of Veterans Affairs Medical Center, Omaha, NE, USA
3 Medicine, University of North Carolina, Chapel Hill, NC, USA
4 Institute for Clinical Chemistry, University of Ulm, Ulm, Germany
5 Pathology, University of Southern California, Los Angeles, CA, USA; Medicine, University of Southern California, Los Angeles, CA, USA; VA Greater Los Angeles Health Care System, Sepulveda, CA, USA
* To whom correspondence should be addressed. E-mail: htsukamo{at}hsc.usc.edu.
Expression of IL-10 is induced in activated hepatic stellate cells (HSC) in vitro and in vivo. To better understand the mechanism of IL-10 mediated regulation of HSC, we analyzed expression of IL-10 receptor (IL-10R) and co-receptor (CRF2-4) in HSC. Specific aims of the present study are: 1) to clone and sequence partial cDNA for rat IL-10R and CRF2-4; 2) to determine expression of IL-10R and CRF2-4 in in vivo and in vitro activated rat HSC; and 3) to 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 the corresponding mouse sequences. Northern blot analysis with a cloned IL-10R cDNA, detected an expected 3.5 kb transcript in hepatic macrophages (HM). In HM, IL-10R and CRF2-4 mRNAs showed steady constitutive expression after in vitro LPS treatment or in cholestatic liver injury. In contrast, IL-10R mRNA expression was induced by 20.1 and 8.6 fold in HSC from cholestatic livers and 7 day culture-activated HSC, respectively while CRF2-4 mRNA levels were unchanged. Increased expression of IL-10R protein in culture-activated HSC was confirmed by immunohistochemistry. In 7 day culture-activated HSC in serum-fee condition, IL-10 had minimal effects on collagen production while reducing DNA synthesis, MMP-2 mRNA level and activity. In serum-stimulated condition, IL-10 inhibited both collagen production and DNA synthesis while having no effects on 
1(I) procollagen mRNA levels. These results demonstrate 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.
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