Cyclooxygenase-2 immunoreactivity in collagenous colitis.

Collagenous colitis (CC) is an inflammatory bowel disease of unknown aetiology and pathogenesis. In ulcerative colitis and Crohn's disease, prostaglandins may be involved in the pathogenesis of inflammation, and increased expression of cyclo-oxygenase-2 (COX-2) has been detected. The purpose of this study was to examine the presence and cellular localization of COX-2 in colonic mucosa of patients with CC. Using immunohistochemistry, immunoflouresence and Western blot analysis, COX-2 expression was evaluated in colonic mucosal biopsies from 10 patients with active untreated CC, and compared with samples from eight normal controls, and samples from eight patients with ulcerative colitis or Crohn's disease. Specimens from patients with CC expressed COX-2 protein in increased amounts compared with controls, but similar to patients with ulcerative colitis and Crohn's disease. COX-2 expression was localized to the mononuclear cells of the lamina propria. COX-2 expression was most evident in macrophages. Co-localization of COX-2 and macrophages was increased in number in comparison with controls. In conclusion COX-2 is expressed in increased amounts primarily in the macrophage subpopulation of the inflammatory infiltrate of lamina propria in CC. Increased recruitment of macrophages, increased expression of COX-2 and increased prostaglandin synthesis may be involved in the pathogenesis of CC.

Expression of inducible nitric oxide synthase and effects of L-arginine on colonic nitric oxide production and fluid transport in patients with "minimal colitis".

OBJECTIVE: Some patients with idiopathic, chronic diarrhoea have minimal, non-specific colonic inflammation. As nitric oxide (NO) acts as a secretagogue in the colon, we studied the expression of inducible NO synthase (iNOS) in mucosal biopsies and the effects of NOS stimulation on colonic transfer of fluid and output of NO in patients with "minimal colitis". MATERIAL AND METHODS: Twelve patients with idiopathic, chronic diarrhoea and "minimal colitis" and 6 healthy volunteers were included in the study. Expression of iNOS in colonic mucosal biopsies was quantified by Western blot analysis and localized by immunohistochemistry. The effects of topical L-arginine or placebo on colonic net fluid transfer and nitrite/nitrate (NOx) output were assessed during "steady state" perfusion of the whole colon. Concentrations of NOx were measured by Griess' assay. RESULTS: The expression of iNOS was increased 10-fold (p<0.01) in patients with "minimal colitis" compared with that in healthy volunteers and localized to the colonic epithelium. Colonic absorption of fluid was impaired (mean (SEM) 1.5 (0.2) versus 3.0 (0.2) ml/min, p<0.001) and the output of NOx was increased (47 (4) nmol/min versus <37 nmol/min, p<0.05) in patients with "minimal colitis" compared with that in healthy volunteers. Luminal L-arginine (20 mM) reduced colonic absorption of fluid in both groups (95% confidence intervals (CIs) 21-50% in patients with "minimal colitis" versus 4-18% in healthy volunteers), but an increase in NOx output was detectable only in the group of patients (8-106%). In time control experiments, colonic net transfer rates of fluid and outputs of NOx were unaffected by placebo. CONCLUSIONS: In patients with idiopathic, chronic diarrhoea and histopathological evidence of "minimal colitis", colonic absorption of fluid is impaired, while epithelial expression of iNOS and mucosal production of NO is enhanced. It could be speculated that NO in excess contributes to the diarrhoea observed in "minimal colitis".