IL-1beta induction of NF-kappaB activation in human intestinal epithelial cells is independent of oxyradical signaling.

Parikh AA, Moon MR, Pritts TA, Fischer JE, Szabó C, Hasselgren PO, Salzman AL
Shock. 2000 13 (1): 8-13

PMID: 10638662 · DOI:10.1097/00024382-200013010-00002

IL-1beta stimulation of cultured epithelial cells induces the degradation of IkappaBalpha and the consequent nuclear translocation of NF-lambdaB, a critical proinflammatory transcription factor in the mucosal host immune response. The role of reactive oxygen intermediates, serine protease activity, and tyrosine kinase activity in the activation of NF-kappaB is weakly conserved across various cell lineages and has not been defined in human enterocytes, a major target of oxidant stress in sepsis, thermal injury, and hemorrhagic shock. We report here that in Caco-2BBe cells, a transformed human colon cancer cell line with features of small intestinal epithelial cells in culture, exposure to oxidant stress (hydrogen peroxide 1-10 mM) did not induce NF-kappaB activation. Similarly, scavenging of free radicals and oxidants by pyrrolidine dithiocarbamate and dimethyl sulfoxide did not block IL-1beta-induced IkappaBalpha degradation and NF-kappaB activation. Genistein, a nonspecific tyrosine kinase inhibitor, also had no effect on IL-1beta-mediated effects on NF-kappaB. Serine protease inhibition by tosyl-lysine-chloromethylketone and tosyl-phenylalanine-chloromethylketone inhibited IkappaBalpha degradation and NF-kappaB activation stimulated by IL-1beta. Our data highlight the strong divergence between epithelial and mononuclear cells in the signal transduction pathways relating IL-1beta stimulation and NF-kappaB nuclear translocation.

MeSH Terms (21)

Adenocarcinoma Antioxidants Cell Nucleus Cell Survival Colonic Neoplasms Dimethyl Sulfoxide DNA-Binding Proteins Free Radical Scavengers Humans Hydrogen Peroxide I-kappa B Proteins Interleukin-1 Intestinal Mucosa NF-kappa B NF-KappaB Inhibitor alpha Oxidants Pyrrolidines Recombinant Proteins Thiocarbamates Transcription Factors Tumor Cells, Cultured

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