Authors: Krishnendu Khan Monica Konar Atul Goyal Sujata Ghosh
Publish Date: 2009/10/24
Volume: 337, Issue: 1-2, Pages: 17-24
Abstract
Enteroaggregative Escherichia coli EAEC is emerging as a cause of acute and persistent diarrhea in developing countries An important feature of EAEC pathogenesis is the induction of profound inflammatory response in the intestinal epithelium In this article we have shown that EAECinduced activation of mitogenactivated protein kinases MAPK ERK1/2 JNK and p38MAPK in cultured human intestinal epithelial cells INT407 leads to the induction of DNAbinding activity of NFκB and AP1 resulting in IL8 production Plasmidcured EAEC could also activate the MAPK and the transcription factors leading to IL8 secretion but to a lesser extent than that of wildtype EAEC Further pretreatment of these cells with the highly specific MEK inhibitor PD 098059 the JNK inhibitor SP 600125 and the p38MAPK inhibitor SB 203580 resulted in inhibition of the IL8 secretion by EAEC wild type as well as plasmid curedinfected INT407 cells These findings demonstrate that the inflammatory response induced by EAEC may be due to the specific stimulation of MAPK signaling pathways leading to nuclear responses To our knowledge this is the first article regarding the detailed mechanism of IL8 secretion from the EAECinfected human intestinal epithelial cell line
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