Inducible nitric oxide synthase in rat hepatic lipocytes and the effect of nitric oxide on lipocyte contractility.
Open Access
- 1 March 1995
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 95 (3), 1199-1206
- https://doi.org/10.1172/jci117769
Abstract
In liver injury, perisinusoidal cells known as lipocytes (Ito cells) undergo "activation," acquiring smooth muscle-like features and a contractile phenotype. To assess whether contraction of these cells is regulated by nitric oxide (NO), we examined the production of NO by lipocytes and the effect of NO on lipocyte contractility. Cultured lipocytes were exposed to cytokines and/or LPS. Single agents had little or no effect on the level of inducible NO synthase (iNOS) mRNA. However, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), or LPS in combination with interferon-gamma (IFN-gamma) stimulated iNOS mRNA, which was present within 4 h after exposure. iNOS mRNA levels were paralleled by changes in nitrite (a metabolic product of NO). Intraperitoneal administration of IFN-gamma, TNF-alpha, and LPS led to rapid induction of iNOS mRNA in lipocytes, confirming in vivo the culture findings. Ligation of the common hepatic bile duct, which induces periportal-based liver injury, stimulated iNOS mRNA in lipocytes. Transforming growth factor-beta 1 decreased IFN-gamma/TNF-alpha--stimulated iNOS mRNA and nitrite. Finally, the effect of NO on lipocyte contractility was examined. In cells incubated with IFN-gamma and TNF-alpha, the contractile response to either serum or endothelin-1 was blocked. Contraction was restored entirely by an inhibitor of NO synthase, NG-monomethylarginine. Furthermore, 8-bromoguanosine 3':5'-cyclic monophosphate and sodium nitroprusside inhibited lipocyte contractility, consistent with the effect of NO induced by cytokines. We conclude that NO is a potent modulator of lipocyte contractility and may regulate this function by autocrine (or intracrine) mechanisms. Moreover, NO may play an important role in liver injury, countering the effect of contractile agonists on lipocytes.Keywords
This publication has 50 references indexed in Scilit:
- Regulation of endothelin‐1 action on the perfused rat liverFEBS Letters, 1993
- Cloning of Inducible Nitric Oxide Synthase in Rat Vascular Smooth Muscle CellsBiochemical and Biophysical Research Communications, 1993
- Effect of endothelin-1 on croton oil-induced granulation tissue in the rat. A pharmacologic and immunohistochemical study.1992
- Nitric oxide, a novel biologic messengerCell, 1992
- Molecular cloning and expression of a cDNA encoding endothelial cell nitric oxide synthase.Journal of Biological Chemistry, 1992
- Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme.Proceedings of the National Academy of Sciences, 1992
- Eicosanoid-mediated contractility of hepatic stellate cellsBiochemical Journal, 1992
- Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase.Journal of Biological Chemistry, 1992
- Rat hepatic lipocytes express smooth muscle actin upon activation in vivo and in culture.1992
- Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells.The Journal of Experimental Medicine, 1989