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

Philippe Mathurin, Shigang Xiong, Kusum K. Kharbanda, Nary Veal, Takeo Miyahara, Kenta Motomura, Richard A. Rippe, Max G. Bachem, Hidekazu Tsukamoto

Research output: Contribution to journalArticle

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Abstract

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-α 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.

Original languageEnglish (US)
Pages (from-to)G981-G990
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume282
Issue number6 45-6
StatePublished - Jun 27 2002

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Interleukin-10 Receptors
Hepatic Stellate Cells
Interleukins
Interleukin-10
Messenger RNA
Complementary DNA
Liver
Collagen
Procollagen
Cytokine Receptors
DNA
Metalloproteases
Serum
Northern Blotting
Lipopolysaccharides
Organism Cloning
Clone Cells
Immunohistochemistry
Macrophages

Keywords

  • Cytokine receptor family 2-4
  • Interleukin-10
  • Liver fibrosis
  • Matrix metalloprotease-13
  • Matrix metalloprotease-2
  • Monocyte-chemoattracting protein-1
  • Procollagen-α (I)

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

IL-10 receptor and coreceptor expression in quiescent and activated hepatic stellate cells. / Mathurin, Philippe; Xiong, Shigang; Kharbanda, Kusum K.; Veal, Nary; Miyahara, Takeo; Motomura, Kenta; Rippe, Richard A.; Bachem, Max G.; Tsukamoto, Hidekazu.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 282, No. 6 45-6, 27.06.2002, p. G981-G990.

Research output: Contribution to journalArticle

Mathurin, P, Xiong, S, Kharbanda, KK, Veal, N, Miyahara, T, Motomura, K, Rippe, RA, Bachem, MG & Tsukamoto, H 2002, 'IL-10 receptor and coreceptor expression in quiescent and activated hepatic stellate cells', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 282, no. 6 45-6, pp. G981-G990.
Mathurin, Philippe ; Xiong, Shigang ; Kharbanda, Kusum K. ; Veal, Nary ; Miyahara, Takeo ; Motomura, Kenta ; Rippe, Richard A. ; Bachem, Max G. ; Tsukamoto, Hidekazu. / IL-10 receptor and coreceptor expression in quiescent and activated hepatic stellate cells. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2002 ; Vol. 282, No. 6 45-6. pp. G981-G990.
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AU - Miyahara, Takeo

AU - Motomura, Kenta

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N2 - 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-α 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.

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