IL-10 receptor and coreceptor expression in quiescent and activated hepatic stellate cells.
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.
Mathurin
Philippe
P
Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles 90089, USA.
Xiong
Shigang
S
Kharbanda
Kusum K
KK
Veal
Nary
N
Miyahara
Takeo
T
Motomura
Kenta
K
Rippe
Richard A
RA
Bachem
Max G
MG
Tsukamoto
Hidekazu
H
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D002779:Cholestasis / Q000276:immunology / Q000503:physiopathology; D024042:Collagen Type I / Q000235:genetics; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D016753:Interleukin-10 / Q000494:pharmacology; D053710:Interleukin-10 Receptor beta Subunit; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018121:Receptors, Cytokine / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics*; D053701:Receptors, Interleukin-10
D001798:Blood Proteins; D018932:Chemokine CCL2; D024042:Collagen Type I; D016895:Culture Media, Serum-Free; C081846:IL10RB protein, human; D053710:Interleukin-10 Receptor beta Subunit; D008562:Membrane Glycoproteins; D011347:Procollagen; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; C507083:Mmp13 protein, rat; D020778:Matrix Metalloproteinase 2