Chronic ethanol feeding increases activation of NADPH oxidase by lipopolysaccharide in rat Kupffer cells: role of increased reactive oxygen in LPS-stimulated ERK1/2 activation and TNF-α production

• DOI: 10.1189/jlb.1005613
• Publication Date: 2006-03-23T01:25:15Z
• Authors: Varsha Thakur; Michele T Pritchard; Megan R McMullen; Qifang Wang; Laura E Nagy
• Keywords: Kupffer cell

Abstract Reactive oxygen species (ROS) contribute to the development of chronic ethanol-induced liver injury. Although ROS modulate activity many signal transduction pathways, molecular targets during ethanol exposure are not well understood. Here, we investigated whether specific ROS-sensitive pathways increased tumor necrosis factor α (TNF-α) production by Kupffer cells after feeding rats. Lipopolysaccharide (LPS) rapidly production, measured dihydrorhodamine fluorescence, in from ethanol- and pair-fed rats, was 2.5-fold greater ethanol-fed compared with pair-fed. Pretreatment diphenyleneiodonium (DPI), which inhibits reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, normalized LPS Rac1-guanosinetriphosphatase (GTPase) p67phox translocation plasma membrane After feeding, Rac1-GTPase already over at baseline remained elevated stimulation. Further, LPS-stimulated enhanced feeding. extracellular signal-regulated kinase (ERK)1/2 p38 phosphorylation, two signaling regulated ROS, were twofold rats controls. However, only ERK1/2 phosphorylation inhibited DPI, also TNF-α pair- These results demonstrate that increases NADPH oxidase-dependent cells. is an important target oxidase-derived cells, contributing