Potential role of nitric oxide in a model of chronic colitis in rhesus macaques

Ribbons, Karen; Zhang, Xiaojing; Thompson, Jane H.; Greenberg, Samantha; Moore, William M.; Kornmeier, Christine; Currie, Mark G.; Lerche, Nicholas W.; Blanchard, Jim; Clark, David A.; Miller, Mark J.S.

doi:10.1016/0016-5085(95)90442-5

Cited by 86 publications

(54 citation statements)

References 14 publications

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“…Increased expression of inducible NO synthase (NOS2) is found in intestinal epithelial cells during the course of intestinal inflammation (18) and in response to stimulation of epithelial cells with a combination of cytokines. Ongoing studies in our laboratory indicate that enteroinvasive bacteria are potent inducers of NOS gene expression and nitric oxide production in intestinal epithelial cells.…”

Section: Repertoire Of Intestinal Epithelial Responsesmentioning

confidence: 99%

Epithelial cells as sensors for microbial infection.

Kagnoff

Eckmann²

1997

J. Clin. Invest.

538

333

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Section: Repertoire Of Intestinal Epithelial Responsesmentioning

confidence: 99%

Epithelial cells as sensors for microbial infection.

Kagnoff

Eckmann²

1997

J. Clin. Invest.

538

333

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“…Although many inflammatory mediators secreted by these cells, including the cytokines IL-1, IL-6, IL-8, IL-10, TNF-␣ , and leukotrienes together with luminal bacterial products such as bacterial lipopolysaccharide (LPS) and the chemotactic peptide fMLP, have been implicated in the mucosal injury observed in IBD (1), the molecules that mediate tissue damage remain poorly understood (2). Recent indirect evidence has, however, implicated reactive oxygen and nitrogen species (RONS) such as nitric oxide (NO), superoxide (O 2 · Ϫ ), peroxynitrite (ONOO Ϫ ), hydrogen peroxide (H 2 O 2 ), and hypochlorite (OCl Ϫ ) in the pathogenesis of the mucosal lesion (3)(4)(5)(6)(7)(8)(9). Increased production of RONS has been observed after in vitro stimulation of whole colonic mucosa, mucosal macrophages, and peripheral blood monocytes of IBD patients (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…Increased production of RONS has been observed after in vitro stimulation of whole colonic mucosa, mucosal macrophages, and peripheral blood monocytes of IBD patients (3)(4)(5). Furthermore, the coproduct of NO generation, citrulline, has been observed at greater than normal levels in the colonic lumen of patients suffering from active IBD (7) and of primates with chronic colitis (9). RONS scavengers and inhibitors of RONS production including superoxide dismutase (10)(11)(12)(13), dimethylsulphoximide, and allopurinol (10), and N G -nitrol -arginine (14) have shown some antiinflammatory effects in limited clinical trials and in animal models of IBD.…”

Section: Introductionmentioning

confidence: 99%

Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease.

et al. 1996

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Evidence of in vivo oxidant-induced injury in inflammatory bowel disease (IBD) is largely indirect. Colon epithelial crypt cells (CEC) from paired specimens of histologically normal and inflamed bowel from IBD patients with active disease were examined for altered protein thiol redox status as an indicator of oxidative damage. When CEC preparations from 22 IBD patients were labeled with the reducedthiol-specific probe [14 C]-iodoacetamide (IAM), there was decreased labeling of a number of proteins indicating oxidation of thiol groups in CEC from inflamed mucosa compared to paired normal mucosa, especially the loss of thiol labeling of a 37-kD protein which was almost completely lost. The loss of reduced protein thiol status for the 37-kD band was paralleled by loss of epithelial cell glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) enzyme activity, an enzyme known to contain an essential reduced cysteine (Cys 149 ) at the active site. The identity of the 37-kD protein as GADPH monomer was confirmed by NH 2 -terminal amino acid sequence analysis.To examine whether this type of in vivo injury could be attributed to biologically relevant oxidants produced by inflammatory cells, CEC prepared from normal mucosa were exposed to H 2 O 2 , OCl

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“…Indeed, authors have reported significant amelioration (Hogaboam et al, 1995;Rachmilewitz et al, 1995b), no protection (Conner et al, 2000), and even further exacerbation (Pfeiffer and Qiu, 1995) in various colonic inflammatory parameters including macroscopic alterations, tissue myeloperoxidase (MPO) activity, or histologic changes. Moreover, in a model of spontaneous chronic colitis in the rhesus monkey, which closely resembles IBD in humans, administration of selective inhibitors of iNOS activity did not provide any therapeutic benefit in terms of macroscopic damage and diarrhea status (Ribbons et al, 1995). Evidence shows that genetically modified mice that specifically lack the iNOS gene develop a more severe colitis than wildtype mice in response to acetic acid (McCafferty et al, 1997) or trinitrobenzene sulfonic acid instillation (McCafferty et al, 1999); this supports the view that NO may play a potential protective role in the inflammatory response during flares of IBD.…”

mentioning

confidence: 93%

Nitric Oxide Supplementation Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice

Salas

Gironella

Salas

et al. 2002

Laboratory Investigation

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SUMMARY:Nitric oxide (NO) synthesis is up-regulated in inflammatory bowel disease. However, its role in the pathophysiology of this condition is controversial. The aims of this study were to assess whether nitric oxide administration ameliorates experimental colitis and to determine the possible mechanisms underlying its effects on intestinal inflammation. For this purpose, the NO donor diethylamine NONOate (DETA/NO; 0.01, 0.1, 1, 5, or 10 mg/kg/day), or the DETA moiety, was administered daily to mice with dextran sulfate sodium-induced colitis. Daily body weight and colonic pathologic alterations at Day 10 were determined. Leukocyte endothelial cell interactions in colonic venules were assessed with intravital microscopy, and expression of endothelial cell adhesion molecules was determined using radiolabeled antibodies. IL-12 and IFN-␥ production were measured in intestinal tissue. Colitis induced a significant loss of body weight, reduction of colon length, and increase in colon weight and myeloperoxidase activity. Administration of 1 mg/kg/day DETA/NO significantly attenuated these pathologic changes. The marked increase in leukocyte rolling and adhesion in colonic venules of colitic mice were significantly reduced by administration of 1 mg/kg/day DETA/NO. Development of colitis was associated with a marked increase in endothelial expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and P-selectin. Supplementation with NO significantly attenuated the up-regulation of endothelial intercellular adhesion molecule-1 and P-selectin, but not vascular cell adhesion molecule-1, in colonic tissue. NO abrogated the increase in IL-12 and IFN-␥ mRNA expression in the colon of colitic mice. The DETA moiety alone did not have any effect on any of the parameters studied. In conclusion, exogenous NO supplementation significantly ameliorates dextran sulfate sodium-induced colitis. This effect is related to a reduction in leukocyte recruitment and proinflammatory cytokine production. (Lab Invest 2002, 82:597-607).

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Potential role of nitric oxide in a model of chronic colitis in rhesus macaques

Cited by 86 publications

References 14 publications

Epithelial cells as sensors for microbial infection.

Epithelial cells as sensors for microbial infection.

Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease.

Nitric Oxide Supplementation Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice

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