Prolonged colonic epithelial hyporesponsiveness after colitis: role of inducible nitric oxide synthase

Abstract

Colonic epithelial secretion is an important host defense mechanism. We examined whether a bout of colitis would produce long-lasting changes in epithelial function that persisted after resolution of mucosal inflammation. Colitis was induced in rats with intracolonic trinitrobenzenesulfonic acid. Six weeks later, colonic damage and inducible nitric oxide synthase (iNOS) mRNA expression and activity were measured. Segments of distal colon were mounted in Ussing chambers for measurement of permeability and responsiveness to secretory stimuli. Basal electrolyte transport parameters and permeability were not different from untreated controls. Despite normal macroscopic and histological appearance, secretory responses to electrical field stimulation (EFS), isobutylmethylxanthine (IBMX), and carbachol were significantly depressed (by 60–70%) relative to controls. iNOS mRNA expression and enzyme activity were significantly elevated. Dexamethasone reversed epithelial hyporesponsiveness and significantly reduced iNOS mRNA expression. A selective iNOS inhibitor normalized the secretory responses to EFS and IBMX but not to carbachol. These data suggest that ongoing synthesis of nitric oxide by iNOS contributes to chronic suppression of epithelial secretory function after episodes of colitis.

Visceral and Somatic Hypersensitivity in TNBS-Induced Colitis in Rats

“…These findings differ from Asfaha et al [37] in which the inflammation peaked at day 3 and then gradually resolved. Our findings may be different as we used Sprague-Dawley rats and not Wistar rats.…”

Anti-Inflammatory Mechanisms of EntericHeligmosomoides polygyrusInfection against Trinitrobenzene Sulfonic Acid-Induced Colitis in a Murine Model

“…This may be due to a direct effect of immune and/or inflammatory mediators on epithelial function or an indirect effect due to the loss of epithelial cells in inflammation. Secretion is an important part of mucosal defense because it facilitates removal of harmful substances and bacteria in the lumen away from the epithelial surface and reduces bacterial translocation (1). In the present study, TNBS uniformly inhibited secretion (I sc ) in responses to all secretagogues tested, although it did not affect resistance, indicating a largely intact barrier function.…”

Tapeworm Infection Reduces Epithelial Ion Transport Abnormalities in Murine Dextran Sulfate Sodium-Induced Colitis

“…Vectorial, electrogenic ion transport creates the driving force for water movement and thus regulates water balance in the intestine, the extremes of which can result in debilitating diarrhea or constipation. Assessment of tissues from other rodent models of colitis and examination of tissue resections from patients with inflammatory bowel disease consistently reveal altered ion transport, typically reduced responses to prosecretory stimuli (4,7,17). Thus, the ability of H. diminuta infection to normalize, at least in part, the colonic ion transport in the face of colitis supports the contention that helminth infection is of benefit in preventing or treating some forms of colitis.…”