Good bug, bad bug: in the case of enteric inflammatory disease does the epithelium decide?
Many studies demonstrate that intestinal inflammation is either initiated or exaggerated by a component of the normal microbiota, most likely commensal bacteria or products derived from these organisms. We review the nature of human inflammatory bowel disease, the evidence for the involvement of the normal bacterial flora in these disorders and the relevance of maintaining the integrity of the epithelial barrier. Moreover, we, and others, have shown abnormal mitochondria structure in tissue resections from patients with inflammatory bowel disease and tissues from rodents that demonstrated psychological stress-induced increases in epithelial permeability. Thus, we also consider the possibility that a defect in epithelial mitochondrial function would predispose an individual to respond to their commensal bacteria flora--no longer considering them as a beneficial passive inhabitant, but rather perceiving them as a threatening and pro-inflammatory stimulus. In support of this postulate, we discuss our recent findings from an in vitro model showing that the human colon-derived T84 cell line exposed to the metabolic stressor, dinitrophenol, and the non-pathogenic, non-invasive, Escherichia coli (strain HB101) display a loss of barrier function, increased signal transduction and increased production of the chemokine, interleukin 8.
McKay
Derek M
DM
Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario L8N 3Z5, Canada. mckayd@mcmaster.ca
D000818:Animals; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000382:microbiology*; D016209:Interleukin-8 / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology*; D010539:Permeability
D016209:Interleukin-8