title: Involvement of intracellular signaling cascades in inflammatory responses in human intestinal epithelial cells following Vibrio cholerae infection.
abstract: Vibrio cholerae, the etiological agent of cholera, leads to the induction of host cell nuclear responses and the activation of proinflammatory cytokines in the cultured intestinal epithelial cells. However, the host cell signaling pathway leading to proinflammatory response is not explored. In this study, we demonstrated that V. cholerae infection on intestinal epithelial cells results in the activation of extracellular signal-regulated kinases1/2(ERK1/2) and p38 of the mitogen activated protein kinase (MAPK) family. V. cholerae induced intracellular pathways in Int407 cells leading to the activation of protein kinase A (PKA) and protein tyrosine kinase (PTK) in upstream of MAPK and nuclear factor-kappaB (NF-kappaB) pathway. Inhibitor study of Ca(2+) and phospholipase-gamma (PLC-gamma) pathway suggested the possible involvement of Ca(2+) signaling in the V. cholerae pathogenesis. V. cholerae culture supernatants as also insertional mutants of ctxA, toxR and toxT genes modulate the activation of MAPK and NF-kappaB signaling pathways. MAPK and NF-kappaB signaling pathway activation were also modulated by adherence and motility of V. cholerae. Studies with inhibitor of NF-kappaB, MAPK, PTK, PKA, PKC, Ca(2+) and PLC pathways showed differential cytokine secretion in Int407 following V. cholerae infection. Therefore V. cholerae mediated induction of nuclear responses through signal transduction pathway and subsequent activation of proinflammatory cytokines in Int407 modulated by V. cholerae secretory factors, virulence, adhesion/motility which might explain some of its reactogenic mechanisms.
authors.affiliation: Molecular and Human Genetics Division, Indian Institute of Chemical Biology (CSIR), 4 Raja S C Mullick Road, Kolkata 700032, India.
authors.forename: Arunava
authors.initials: A
authors.lastname: Bandyopadhaya
authors.forename: Debalina
authors.initials: D
authors.lastname: Das
authors.forename: Keya
authors.initials: K
authors.lastname: Chaudhuri
mesh_terms: D001422:Bacterial Adhesion; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002771:Cholera / Q000276:immunology* / Q000382:microbiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009154:Mutation; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014734:Vibrio cholerae / Q000235:genetics / Q000276:immunology / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D016328:NF-kappa B; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D051966:Phospholipase C gamma; D002118:Calcium