PMID: 9544582Apr 17, 1998Paper

Inhibition of LPS-mediated activation in rat Kupffer cells by N-acetylcysteine occurs subsequent to NF-kappaB translocation and requires protein synthesis

Journal of Leukocyte Biology
E S Fox, K A Leingang

Abstract

Activation of the resident hepatic macrophage population, Kupffer cells, leads to production of mediators that initiate, potentiate, and modulate hepatic injury. Recent studies have shown that activation of the pluripotent transcription factor nuclear factor-kappaB (NF-kappaB) is an important step in the induction of inflammatory cytokines, chemokines, growth factors, cell adhesion proteins, and cytokine receptors, thus efforts have been focused to modulate its activity. A common observation in diverse experimental systems is that oxidant stress activates NF-kappaB and antioxidant drugs prevent activation and subsequent inflammatory gene transcription. However, we have recently shown that the inhibitory effect of N-acetylcysteine (NAC) is independent of its role as a substrate of glutathione synthesis and NAC can inhibit Kupffer cell activation at points beyond the initiation of activation. The goal of this study was to characterize the mechanism for NAC-mediated inhibition of Kupffer cell activation. We show for the first time that this process requires a cellular synthetic response to prevent both NF-kappaB and tumor necrosis factor alpha (TNF-alpha) mRNA activation. Furthermore, NAC-mediated inhibition occurs after degradati...Continue Reading

Citations

Jan 11, 2003·Journal of Toxicology and Environmental Health. Part a·Ramez LabibRita Turkall
Nov 4, 2011·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Ron BelooseskyMichael G Ross
May 28, 2011·Journal of Drug Targeting·Caroline BuonocoreZacharias E Suntres
Mar 15, 2003·The Journal of Biological Chemistry·Shigang XiongHidekazu Tsukamoto
Aug 8, 2008·Current Opinion in Clinical Nutrition and Metabolic Care·Anja SandekStephan von Haehling
Nov 27, 1999·The Journal of Biological Chemistry·H PyoI Jou
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Mar 23, 2004·The Veterinary Clinics of North America. Small Animal Practice·Sharon A Center

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