Abstract

We investigated differences in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis between two inbred rat strains, Wistar King A Hokkaido (WKAH) and Dark Agouti (DA) rats, to determine the intrinsic factors responsible for the development of colitis. DSS exposure exacerbated the clinical symptoms such as body weight loss, stool consistency and rectal bleeding in DA rats rather than that in WKAH rats. Additionally, the average survival was shorter in DA rats than in WKAH rats. The expression levels of tumor necrosis factor-α, interleukin (IL)-12 p35 and IL-23 p19 increased prominently in the DA rats that were administered DSS, accompanied by severe infiltration of leukocytes into the colon. We also found that colonic permeability was greater in the DA rats than in the WKAH rats. In Ussing chambers, exposure of the isolated colon tissue to DSS enhanced the colonic permeability of both strains. Immunoblot analysis revealed that the expression levels of tight junction (TJ) proteins were modulated during DSS administration. Higher expression levels of claudin-4 and junctional adhesion molecule-A proteins were observed in DA rats than in WKAH rats, even in intact conditions. These results indicated that the expression pattern of TJ proteins determines the colonic permeability of the rats. In conclusion, the intrinsic colonic permeability is one of critical factors responsible for the susceptibility of rats to colitis.

Links

Publisher Full Text

Authors

Iwaya H, Maeta K, Hara H, Ishizuka S

Institution

Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University, Sapporo 060-8589, Japan.

Source

Experimental biology and medicine (Maywood, N.J.) 237:4 2012 Apr pg 451-60

MeSH

Animals
Colitis
Colon
Dextran Sulfate
Disease Models, Animal
Intestinal Mucosa
Male
Membrane Proteins
Permeability
Phosphorylation
Rats
Rats, Inbred Strains
Species Specificity
Tight Junctions

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22522346