Colonic epithelial physiology is altered in response to the bacterial superantigen Yersinia pseudotuberculosis mitogen.
Because bacteria are implicated in the pathophysiology of gut inflammation, the ability of the superantigen Yersinia pseudotuberculosis mitogen (YPM) to alter epithelial ion transport and permeability was examined by two model systems: epithelial (T84) monolayers cocultured with peripheral blood mononuclear cells (PBMC) with or without YPM and colonic segments from YPM-treated mice. YPM immune activation in vitro caused reduced active ion transport responses to the prosecretory agent forskolin (increases cAMP) and increased permeability. Similar changes in T84 function were evoked by conditioned medium (CM) from YPM-activated PBMC, and tumor necrosis factor-alpha and interferon-gamma were mediators of these events. Inclusion of piroxicam in the CM prevented increases in epithelial permeability but did not ameliorate the perturbed ion transport. Colonic tissue from YPM-treated mice displayed diminished responsiveness to cAMP-mediated secretagogues and nerve stimulation. Thus, Y. pseudotuberculosis enteric symptomatology may be at least partially due to YPM, and superantigens have the potential to initiate or exacerbate gut dysfunction.
Donnelly
G A
GA
Intestinal Disease Research Programme, McMaster University, Hamilton, Canada.
Lu
J
J
Takeda
T
T
McKay
D M
DM
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D015011:Yersinia pseudotuberculosis / Q000276:immunology*
D001426:Bacterial Proteins; D017077:Culture Media, Conditioned; D016207:Cytokines; D008934:Mitogens; D018089:Superantigens; C093313:Yersinia pseudotuberculosis-derived mitogen; D005576:Colforsin