BACKGROUND: Nitric oxide (NO) synthesis and inducible nitric oxide synthase (iNOS) expression are increased in colonic biopsy specimens from patients with ulcerative colitis, but the cellular source of NO production is not known. AIMS: To examine the distribution of iNOS in human colonic mucosa and to explore the ability of T lymphocyte derived cytokines to regulate iNOS expression and activity in human colonic epithelial cells. METHODS: iNOS expression was examined using immunohistochemistry in colonic biopsy samples from 12 patients with ulcerative colitis and three with infectious colitis and compared with 10 normal controls. In vitro iNOS expression and activity were determined in HT-29 cell cultures; nitrite levels were measured using a fluorescent substrate, iNOS mRNA expression by northern blot analysis, and iNOS protein expression by western blot analysis. RESULTS: No iNOS expression was detected (10 of 10) in non-inflamed mucosa derived from normal controls. In 11 of 12 cases of newly diagnosed ulcerative colitis, iNOS protein was expressed in the epithelial cells, while no other positive cells were found in the lamina propria. Similar iNOS labelling was found in colonic biopsy samples from patients with infectious colitis in the acute phase, but when re-examined in samples from patients in total remission, no iNOS staining was observed. Both interleukin (IL)-13 and IL-4, but not IL-10, are potent inhibitors of iNOS expression and activity induced by an optimal combination of cytokines, namely IL-1 alpha, tumour necrosis factor alpha and interferon gamma. CONCLUSIONS: The data suggest that the epithelium is the major source of iNOS activity in ulcerative colitis and that IL-13 and IL-4 may act as intrinsic regulators of NO generation in intestinal inflammation.
BACKGROUND:Nitric oxide (NO) synthesis and inducible nitric oxide synthase (iNOS) expression are increased in colonic biopsy specimens from patients with ulcerative colitis, but the cellular source of NO production is not known. AIMS: To examine the distribution of iNOS in humancolonic mucosa and to explore the ability of T lymphocyte derived cytokines to regulate iNOS expression and activity in human colonic epithelial cells. METHODS:iNOS expression was examined using immunohistochemistry in colonic biopsy samples from 12 patients with ulcerative colitis and three with infectious colitis and compared with 10 normal controls. In vitro iNOS expression and activity were determined in HT-29 cell cultures; nitrite levels were measured using a fluorescent substrate, iNOS mRNA expression by northern blot analysis, and iNOS protein expression by western blot analysis. RESULTS: No iNOS expression was detected (10 of 10) in non-inflamed mucosa derived from normal controls. In 11 of 12 cases of newly diagnosed ulcerative colitis, iNOS protein was expressed in the epithelial cells, while no other positive cells were found in the lamina propria. Similar iNOS labelling was found in colonic biopsy samples from patients with infectious colitis in the acute phase, but when re-examined in samples from patients in total remission, no iNOS staining was observed. Both interleukin (IL)-13 and IL-4, but not IL-10, are potent inhibitors of iNOS expression and activity induced by an optimal combination of cytokines, namely IL-1 alpha, tumour necrosis factor alpha and interferon gamma. CONCLUSIONS: The data suggest that the epithelium is the major source of iNOS activity in ulcerative colitis and that IL-13 and IL-4 may act as intrinsic regulators of NO generation in intestinal inflammation.
Authors: N K Boughton-Smith; S M Evans; C J Hawkey; A T Cole; M Balsitis; B J Whittle; S Moncada Journal: Lancet Date: 1993-08-07 Impact factor: 79.321
Authors: R de Waal Malefyt; C G Figdor; R Huijbens; S Mohan-Peterson; B Bennett; J Culpepper; W Dang; G Zurawski; J E de Vries Journal: J Immunol Date: 1993-12-01 Impact factor: 5.422
Authors: P Manousou; G Kolios; V Valatas; I Drygiannakis; L Bourikas; K Pyrovolaki; I Koutroubakis; H A Papadaki; E Kouroumalis Journal: Clin Exp Immunol Date: 2010-11 Impact factor: 4.330
Authors: Tryggve Ljung; Sofie Lundberg; Mark Varsanyi; Catharina Johansson; Peter T Schmidt; Max Herulf; Jon O Lundberg; Per M Hellstrom Journal: World J Gastroenterol Date: 2006-06-07 Impact factor: 5.742