title: Prolonged NF-κB activation by a macrophage inhibitory cytokine 1-linked signal in enteropathogenic Escherichia coli-infected epithelial cells.
abstract: Intestinal epithelial activation of nuclear factor kappa B (NF-κB) exerts both detrimental and beneficial functions in response to various luminal insults, including ones associated with mucosa-associated pathogens. Gastrointestinal infection with enteropathogenic Escherichia coli (EPEC) causes severe injuries in epithelial integrity and leads to watery diarrhea. The present study was conducted to investigate the prolonged epithelial responses to persistent EPEC infection via NF-κB activation. EPEC infection led to sustained activation of NF-κB signal in mouse intestinal epithelial cells in vivo and in vitro, which was positively associated with a type III secretion system, whereas early NF-κB is regulated. Moreover, prolonged NF-κB activation was found to be a part of macrophage inhibitory cytokine 1 (MIC-1)-mediated signaling activation, a novel link between NF-κB signaling and infection-associated epithelial stress. EPEC infection induced gene expression of MIC-1, a member of the transforming growth factor β (TGF-β) superfamily, which then activated TGF-β-activated kinase 1 and consequently led to NF-κB activation. Functionally, both EPEC-induced MIC-1 and NF-κB signaling mediated epithelial survival by enhancing the expression of cyclin D1, a target of NF-κB. In summary, the results of the present study suggest that MIC-1 serves as a mediator of prolonged NF-κB activation, which is critical in maintaining gut epithelial integrity in response to infection-induced injuries.
authors: Laboratory of Mucosal Exposome and Biomodulation, Department of Microbiology and Immunology, Medical Research Institute, Pusan National University School of Medicine, Yangsan, South Korea.
authors: Hye Jin
authors: HJ
authors: Choi
authors: Juil
authors: J
authors: Kim
authors: Kee Hun
authors: KH
authors: Do
authors: Seong-Hwan
authors: SH
authors: Park
authors: Yuseok
authors: Y
authors: Moon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D054308:Enteropathogenic Escherichia coli / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D055436:Growth Differentiation Factor 15; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C481053:TAB3 protein, human; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; D019938:Cyclin D1
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