Brief hypoxic stress downregulates E. coli-induced IL-1 alpha and IL-1 beta gene expression in perfused liver

The American Journal of Physiology
G M MatuschakA J Lechner

Abstract

Hepatic cytokine gene expression is independently stimulated by circulating microbial products and reductions in the cellular O2 supply. Although these stimuli occur sequentially after gram-negative bacteremia, it is unknown whether their interplay augments production of interleukin (IL)-1 by the liver. We studied the effects of intraportal Escherichia coli (EC) bacteremia and secondary constant-flow hypoxia (Po2, approximately 46 Torr for 30 min) on IL-1 alpha and IL-1 beta gene expression in ex situ buffer-perfused rat livers over 180 min (n = 67). At t = 0, normoxic EC and normal saline (NS) controls received 10(9) live EC serotype 055:B5 and 0.9% NaCl, respectively; in livers subjected to EC+hypoxia-reoxygenation (H/R) and NS+H/R, hypoxia began 0.5 h after EC or NS and was followed by 120 min of reoxygenation. Portal and hepatic venous perfusates were serially analyzed for bacterial colony-forming units, O2 uptake, and aspartate aminotransferase. At 60 min (peak hypoxia) and 180 min, cDNAs for IL-1 alpha and IL-1 beta were hybridized to whole liver RNA, and IL-1 beta protein levels in venous perfusates were assessed. Intrahepatic levels of reduced glutathione (GSH) were measured as an index of oxidative stress. Compared wit...Continue Reading

Citations

Jul 18, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·L L LoftisG M Matuschak
Apr 3, 2004·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·George M MatuschakLaura L Loftis
May 17, 2001·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·W J Becker, J G Cannon
Jun 3, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·M M NdengeleG M Matuschak

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