Intestinal permeability is increased in a proportion of spouses of patients with Crohn's disease

Breslin, Niall; Nash, Carla; Hilsden, Robert J.; Hershfield, Noel B.; Price, Lorne M.; Meddings, Jonathan B.; Sutherland, Lloyd R.

doi:10.1111/j.1572-0241.2001.04684.x

Cited by 65 publications

(27 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This idea is certainly consistent with the recent observations by Swidsinski and colleagues (29). Alternatively, alterations in barrier function (30,31) or intrinsic innate immune responses (32,33) may enhance the likelihood of the response to these flagellin molecules in patients prone to develop IBD.…”

Section: Discussionsupporting

confidence: 79%

Bacterial flagellin is a dominant antigen in Crohn disease

et al. 2004

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 79%

Bacterial flagellin is a dominant antigen in Crohn disease

et al. 2004

View full text Add to dashboard Cite

“…Thus, the epithelium must form a selectively permeable barrier that allows absorption of nutrients, electrolytes, and water while preventing passage of noxious luminal contents. This barrier is disrupted in many diseases, including inflammatory bowel disease, graft versus host disease, and infectious enterocolitis (1)(2)(3)(4)(5)(6). While some have suggested that this barrier dysfunction is a central component of disease pathogenesis (7)(8)(9), other work suggests that barrier dysfunction may be a secondary event that does not contribute to disease progression (10).…”

Section: Introductionmentioning

confidence: 99%

Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo

Clayburgh

Barrett²,

Tang³

et al. 2005

Journal of Clinical Investigation

365

455

View full text Add to dashboard Cite

Disruption of the intestinal epithelial barrier occurs in many intestinal diseases, but neither the mechanisms nor the contribution of barrier dysfunction to disease pathogenesis have been defined. We utilized a murine model of T cell-mediated acute diarrhea to investigate the role of the epithelial barrier in diarrheal disease. We show that epithelial barrier dysfunction is required for the development of diarrhea. This diarrhea is characterized by reversal of net water flux, from absorption to secretion; increased leak of serum protein into the intestinal lumen; and altered tight junction structure. Phosphorylation of epithelial myosin II regulatory light chain (MLC), which has been correlated with tight junction regulation in vitro, increased abruptly after T cell activation and coincided with the development of diarrhea. Genetic knockout of long myosin light chain kinase (MLCK) or treatment of wild-type mice with a highly specific peptide MLCK inhibitor prevented epithelial MLC phosphorylation, tight junction disruption, protein leak, and diarrhea following T cell activation. These data show that epithelial MLCK is essential for intestinal barrier dysfunction and that this barrier dysfunction is critical to pathogenesis of diarrheal disease. The data also indicate that inhibition of epithelial MLCK may be an effective non-immunosuppressive therapy for treatment of immune-mediated intestinal disease.

show abstract

“…The maintenance of the mucosal barrier integrity is believed to be fundamental in preventing the induction of dysregulated immunity induced by microbes and other luminal components. The importance of the mucosal barrier in the pathogenesis of IBD is supported by the findings that intestinal permeability is altered in some first-degree relatives with Crohn's disease and that intestinal permeability precedes a flare of IBD (9,17,51). We have previously shown that trefoil factor (TFF) peptides contribute to mucosal barrier function by protecting the gastrointestinal mucosa from injury and promoting repair after an injury has occurred (2,13,14,23,35).…”

mentioning

confidence: 75%

Exploring the interplay of barrier function and leukocyte recruitment in intestinal inflammation by targeting fucosyltransferase VII and trefoil factor 3

Beck

Ihara

Hirota

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Intestinal mucosal integrity is dependent on epithelial function and a regulated immune response to injury. Fucosyltransferase VII (Fuc-TVII) is an essential enzyme required for the expression of the functional ligand for E- and P-selectin. Trefoil factor 3 (TFF3) is involved in both protecting the intestinal epithelium against injury as well as aiding in wound repair following injury. The aim of the present study was to assess the interplay between barrier function and leukocyte recruitment in intestinal inflammation. More specifically, we aimed to examine how targeted disruption of Fuc-TVII either in wild-type or TFF3−/− mice would alter their susceptibility to colonic injury. TFF3 and Fuc-TVII double-knockout mice (TFF3/Fuc-TVII−/− mice) were generated by mating TFF3−/− and Fuc-TVII−/− mice. Colitis was induced by administration of dextran sodium sulfate (DSS) (2.5% wt/vol) in the drinking water. Changes in baseline body weight, diarrhea, and fecal blood were assessed daily. Upon euthanasia, extents of colonic inflammation were assessed macroscopically, microscopically, and through quantification of myeloperoxidase (MPO) activity. Colonic lymphocyte subpopulations were assessed at 6 days after administration of DSS by flow cytometry and immunohistochemistry. No baseline intestinal inflammation was found in TFF3/Fuc-TVII−/−, TFF3−/−, Fuc-TVII−/−, or wild-type mice. Loss of Fuc-TVII resulted in a reduction in disease severity whereas TFF3−/− mice were markedly more susceptible to DSS-induced colitis. Remarkably, the loss of Fuc-TVII in TFF3−/− mice markedly decreased the severity of DSS-induced colitis as evidenced by reduced weight loss, diarrhea, decreased colonic MPO levels and improved survival. Furthermore, the loss of TFF3 resulted in increased severity of spontaneous colitis in IL-2/β-microglobulin-deficient mice. These studies highlight the importance of the interplay between factors involved in the innate immune response, mucosal barrier function, and genes involved in regulating leukocyte recruitment and other aspects of the immune response.

show abstract

Intestinal permeability is increased in a proportion of spouses of patients with Crohn's disease

Cited by 65 publications

References 40 publications

Bacterial flagellin is a dominant antigen in Crohn disease

Bacterial flagellin is a dominant antigen in Crohn disease

Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo

Exploring the interplay of barrier function and leukocyte recruitment in intestinal inflammation by targeting fucosyltransferase VII and trefoil factor 3

Contact Info

Product

Resources

About