Polarized secretion of CXC chemokines by human intestinal epithelial cells in response to Bacteroides fragilis enterotoxin: NF-kappa B plays a major role in the regulation of IL-8 expression.
Enterotoxigenic B. fragilis, which produces a approximately 20 kD heat-labile toxin (BFT), has been associated with diarrhoeal diseases and mucosal inflammation. To determine if epithelial cells can contribute to BFT-induced inflammation, we assessed the expression of CXC chemokines by BFT-stimulated human intestinal epithelial cells. BFT stimulation increased expression of the neutrophil chemoattractant and activators ENA-78, GRO-alpha, and IL-8. Up-regulated chemokine mRNA expression was paralleled by increased protein levels. Activation of the IL-8 and NF-kappa B transcriptional reporters was inhibited in cells cotransfected with the I kappa B kinase beta and IkB alpha superrepressor plasmids. Whereas lactate dehydrogenase, which was used to monitor cell lysis, was released predominantly from the apical surface, CXC chemokines were predominantly secreted from the basolateral surface of BFT-treated epithelial cells. The basolateral secretion of CXC chemokines from BFT-stimulated colon epithelial cells suggests that these chemokines can contribute to the inflammatory cell infiltrate in the underlying intestinal mucosa.
Kim
J M
JM
Department of Microbiology, Hanyang University College of Medicine, Seoul, Korea. jungmogg@email.hanyang.ac.kr
Oh
Y K
YK
Kim
Y J
YJ
Oh
H B
HB
Cho
Y J
YJ
D001427:Bacterial Toxins / Q000494:pharmacology*; D002460:Cell Line; D016764:Cell Polarity; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology*; D008666:Metalloendopeptidases / Q000494:pharmacology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000032:analysis
D001427:Bacterial Toxins; C475829:CXCL1 protein, human; C486263:CXCL5 protein, human; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D004268:DNA-Binding Proteins; D006133:Growth Substances; D020672:I-kappa B Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C405031:Bacteroides fragilis toxin; D008666:Metalloendopeptidases