IL‐1&bgr; INDUCTION OF NF‐&kgr;B ACTIVATION IN HUMAN INTESTINAL EPITHELIAL CELLS IS INDEPENDENT OF OXYRADICAL SIGNALING
作者:
Alexander Parikh,
Ryan Moon,
Timothy Pritts,
Josef Fischer,
Csaba Szabó,
Per‐Olof Hasselgren,
Andrew Salzman,
期刊:
Shock
(OVID Available online 2000)
卷期:
Volume 13,
issue 1
页码: 8-13
ISSN:1073-2322
年代: 2000
出版商: OVID
关键词: mucosa;inflammation;cytokines;transcription factor;sepsis
数据来源: OVID
摘要:
ABSTRACT—IL‐1&bgr; stimulation of cultured epithelial cells induces the degradation of I&kgr;B&agr; and the consequent nuclear translocation of NF‐&lgr;B, 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‐&kgr;B 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‐&kgr;B activation. Similarly, scavenging of free radicals and oxidants by pyrrolidine dithiocarbamate and dimethyl sulfoxide did not block IL‐1&bgr;‐induced I&kgr;B&agr; degradation and NF‐&kgr;B activation. Genistein, a nonspecific tyrosine kinase inhibitor, also had no effect on IL‐1&bgr;‐mediated effects on NF‐&kgr;B. Serine protease inhibition by tosyl‐lysine‐chloromethylketone and tosyl‐phenylalanine‐chloromethylketone inhibited I&kgr;B&agr; degradation and NF‐&kgr;B activation stimulated by IL‐1&bgr;. Our data highlight the strong divergence between epithelial and mononuclear cells in the signal transduction pathways relating IL‐1&bgr; stimulation and NF‐&kgr;B nuclear translocation.
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