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Colonic epithelial physiology is altered in response to the bacterial superantigen Yersinia pseudotuberculosis
1Intestinal Disease Research Programme, McMaster University, Hamilton, Canada.
Abstract:
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.
Insights
The superantigen Yersinia pseudotuberculosis mitogen (YPM) disrupts gut epithelial function, impairing ion transport and increasing permeability. This suggests YPM contributes to Yersinia-induced gut inflammation and dysfunction.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Bacteria play a role in gut inflammation.
- Superantigens are potent immune activators.
Purpose of the Study:
- To investigate how Yersinia pseudotuberculosis mitogen (YPM) affects gut epithelial ion transport and permeability.
- To determine the role of YPM in Yersinia-induced gut symptoms.
Main Methods:
- Using T84 epithelial cell monolayers co-cultured with peripheral blood mononuclear cells (PBMC) with or without YPM.
- Analyzing colonic segments from YPM-treated mice.
- Assessing responses to forskolin, conditioned medium (CM), tumor necrosis factor-alpha, interferon-gamma, and piroxicam.
Main Results:
- YPM immune activation in vitro reduced active ion transport and increased epithelial permeability.
- Mediators like tumor necrosis factor-alpha and interferon-gamma were involved.
- Piroxicam prevented permeability increases but not transport changes.
- YPM-treated mouse colons showed reduced responsiveness to secretagogues and nerve stimulation.
Conclusions:
- YPM contributes to Yersinia-induced gut symptomatology.
- Superantigens can initiate or worsen gut dysfunction.