PMID: 2121110Oct 1, 1990Paper

Multiple cytokines are required to induce hepatocyte nitric oxide production and inhibit total protein synthesis

Annals of Surgery
R D CurranR L Simmons

Abstract

The etiology and mechanisms by which severe trauma or sepsis induce hepatic failure are unknown. Previously we showed that Kupffer cells (KC), the fixed macrophages of the liver, induce a profound decrease in hepatocyte (HC) total-protein synthesis when exposed to endotoxin. Furthermore we demonstrated that endotoxin-activated KCs induce these changes in HC protein synthesis through the induction of a novel L-arginine-dependent biochemical pathway within the HC. In this pathway, the guanido nitrogen of L-arginine is converted to the highly reactive molecule nitric oxide (NO.). To identify the KC factors that act as signals for induction of HC NO. biosynthesis, recombinant cytokines were added to HC cultures and HC nitrogen oxide production and protein synthesis levels were determined. We found that no single cytokine, but rather a specific combination of tumor necrosis factor, interleukin-1, interferon-gamma, and endotoxin, were required for maximal induction of HC nitrogen oxide production. This specific combination of cytokines induced a 248.8 +/- 26.0 mumol/L (micromolar) increase in HC nitrogen oxide production and simultaneously inhibited HC total protein synthesis by 36.1% +/- 3.1%. These data demonstrate that multiple cy...Continue Reading

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Citations

Feb 14, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S KakumitsuK Inoue
Mar 21, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·R A SchroederP C Kuo
May 15, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·H W HarrisP Chau
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Apr 1, 2000·Clinical and Experimental Pharmacology & Physiology·S SatoiH Takahashi
Oct 24, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kerstin KoerberGisa Tiegs
Dec 11, 2002·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Rahul S KotiAlexander M Seifalian
Jul 27, 1999·Surgery·W BarthlenJ Stadler
Jul 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·M S MulliganP A Ward
Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D A GellerT R Billiar
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