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United States Department of Agriculture

Agricultural Research Service

Title: Transforming Growth Factor B1 Ameliorates Intestinal Epithelial Barrier Disruption by Cryptosporidium Parvum in Vitro in the Absence of Mucosal T Lymphocytes

Authors
item Roche, James - UNIVERSITY OF VIRGINIA
item Martins, Clovis - UNIVERSITY OF VIRGINIA
item Cosme, Rosana - UNIVERSITY OF VIRGINIA
item Fayer, Ronald
item Guerrant, Richard - UNIVERSITY OF VIRGINIA

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 1, 2000
Publication Date: October 1, 2000

Interpretive Summary: When cryptosporidiosis, a protozoan disease of livestock and humans, damages the cells lining the intestinal tract, the barrier function is lost and secondary infection with bacteria and other pathogens can result. The present study has shown that barrier preserving effects result from Transforming Growth Factor beta 1 (TGF-b1) exposure to the base and sides of cells. TGF-b1 activates the protein C enzyme pathway and that in turn reduces the permeability of surface epithelial cells. Understanding how the barrier is preserved provides a basis for developing future preventative and therapeutic methods for preventing or ameliorating cryptosporidiosis and similar diseases.

Technical Abstract: Cryptosporidiosis initiated intestinal mucosal injury can be serious in itself or can additionally facilitate secondary pathogen infection leading to severe morbidity or mortality. Challenge infection with Cryptosporidium parvum of cultured human colonic cells led to disruption of the intestinal epithelial barrier function. Addition of TGF-b1 alone enhanced barrier function. Baso-lateral pretreatment of cells at with TGF-b1 at 5 ng/ml almost completely blocked the disruptive effect of the parasite on barrier function by inducing protein kinase C pathway activation which decreased epithelial cell necrosis by 50%. These findings indicate the importance of the cytokine TGF-b1 in the production of extracellular matrix proteins that maintain intercellular tight junctions and basement membrane for barrier function against cryptosporidial infection.

Last Modified: 12/20/2014
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