Expression of iNOS mRNA associated with suppression of colonic contraction in rat colitis

Lundberg, Steffan; Holst, Mikael; Hellström, Per M.

doi:10.1111/j.1748-1716.2006.01576.x

Cited by 21 publications

(21 citation statements)

References 37 publications

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“…However, in our experimental protocol, where an anticancer agent is administered, we found an increased intestinal contractility veriWed in vitro and that the modulation of the underlying inXammation with genetic depletion of iNOS or treatment with aminoguanidine ameliorated the over-contractility due to irinotecan injection in a more eVective manner than did loperamide, probably because the chronic exposure to the latter is involved with tolerance [54]. Opposingly, Lundberg et al [55] showed that the induced overproduction of NO is likely to be responsible for the decreased motility in colitis where NO is suggested to exert a suppressive tone on colonic contractility, which is reversed by blockade of the enzyme. Until now, it is not clear whether in our model, the higher responsiveness of intestinal samples to the acetylcholine could be due to increased cholinergic receptor expression or a result of local inXammation mediated by cytokines and NO, which merits further investigation.…”

Section: Discussionmentioning

confidence: 46%

Involvement of nitric oxide on the pathogenesis of irinotecan-induced intestinal mucositis: role of cytokines on inducible nitric oxide synthase activation

Lima-Júnior

Figueiredo

Freitas

et al. 2011

Cancer Chemother Pharmacol

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Section: Discussionmentioning

confidence: 46%

Involvement of nitric oxide on the pathogenesis of irinotecan-induced intestinal mucositis: role of cytokines on inducible nitric oxide synthase activation

Lima-Júnior

Figueiredo

Freitas

et al. 2011

Cancer Chemother Pharmacol

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“…Increased expression of iNOS has been reported in inflamed colonic IBD tissue [34][35][36] which may be beneficial during acute inflammation though potentially detrimental if upregulation is sustained [24]. Lack of iNOS, however, has been implicated in the development of polyps and dysplasia in the IL10(-/-) murine model of IBD, suggesting that iNOS may be protective for the development of colonic malignancy [37].…”

Section: Discussionmentioning

confidence: 93%

Wnt Pathway-Related Gene Expression in Inflammatory Bowel Disease

et al. 2007

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The purpose of this study was to examine the expression of Wnt pathway-related genes in patients with ulcerative colitis (UC). RNA from colonoscopic biopsies from noninflammatory bowel disease (non-IBD) subjects and UC patients were obtained and examined with a Wnt-specific microarray for the expression of Wnt pathway-related genes. Paired samples from uninflamed and inflamed areas of the colon were obtained for the UC patients. WNT2B, WNT3A, WNT5B, WNT6, WNT7A, WNT9A, and WNT11 exhibited significantly increased expression in UC compared to non-IBD patients. Frizzled 3 (FZD3) and FZD4 exhibited significantly increased expression, and FZD1 and FZD5 exhibited significantly decreased expression in UC patients. Genes with increased expression in inflamed mucosa included DKK4, DVL2, SOX17, and COL1A1. There was no difference in the expression of a panel of Wnt target genes. The expression of inducible nitric oxide synthase (INOS) was variably influenced by inflammation. Significant differences in extracellular and cell-surface components of the Wnt pathway exist in the colonic mucosa of patients with UC compared with non-IBD patients, which may influence the strength or specificity of Wnt signaling. In inflammation, inhibitory components of the Wnt pathway exhibit increased expression, but no changes in Wnt pathway target gene expression are seen. The role and complex regulation of Sox17 and iNOS in IBD warrant further investigation.

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“…Oxidative stress is a characteristic feature of IBD (27, 28) and inducible nitric oxide synthase (iNOS) expression is an established marker of inflammation and oxidative stress (29). We have previously demonstrated that NPY −/− mice exhibit less nitrosative stress and hence attenuated inflammation compared to WT.…”

Section: Resultsmentioning

confidence: 99%

Tumor Necrosis Factor–Neuropeptide Y Cross Talk Regulates Inflammation, Epithelial Barrier Functions, and Colonic Motility

Chandrasekharan

Jeppsson

Pienkowski

et al. 2013

Inflammatory Bowel Diseases

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Background Neuro-immune interactions play a significant role in regulating the severity of inflammation. Our previous work demonstrated that neuropeptide Y (NPY) is up regulated in the enteric nervous system (ENS) during murine colitis, and that NPY knockout mice exhibit reduced inflammation. Here we investigated if NPY expression during inflammation is induced by tumor necrosis factor (TNF), the main pro-inflammatory cytokine. Methods Utilizing primary enteric neurons and colon explant cultures from WT and NPY knockout (NPY−/−) mice, we determined if NPY knockdown modulates TNF release and epithelial permeability. Further we assessed if NPY expression is inducible by TNF in enteric neuronal cells and mouse model of experimental colitis, utilizing the TNF inhibitors-etanercept (blocks transmembrane and soluble TNF) and XPro1595 (blocks soluble TNF only). Results We found that enteric neurons express TNF receptors (TNFR1 and R2). Primary enteric neurons from NPY−/− mice produced less TNF compared to WT. Further, TNF activated NPY promoter in enteric neurons via phospho-c-jun. NPY−/− mice had decreased intestinal permeability. In vitro, NPY increased epithelial permeability via phosphatidyl inositol-3-kinase (PI3-K)-induced pore-forming claudin-2. TNF inhibitors attenuated NPY expression in vitro and in vivo. TNF-inhibitor-treated colitic mice exhibited reduced NPY expression and inflammation, reduced oxidative stress, enhanced neuronal survival and improved colonic motility. XPro1595 had more protective effects on neuronal survival and motility compared to etanercept. Conclusions We demonstrate a novel TNF-NPY cross talk that modulates inflammation, barrier functions and colonic motility during inflammation. It is also suggested that selective blocking of soluble TNF maybe a better therapeutic option than using anti-TNF antibodies.

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Expression of iNOS mRNA associated with suppression of colonic contraction in rat colitis

Abstract: Expression of iNOS is increased in inflamed colonic tissue. The induced overproduction of NO is likely to be responsible for the decreased motility in colitis where NO is suggested to exert a suppressive tone on colonic contractility, which is reversed by blockade of the enzyme.

Cited by 21 publications

References 37 publications

Involvement of nitric oxide on the pathogenesis of irinotecan-induced intestinal mucositis: role of cytokines on inducible nitric oxide synthase activation

Involvement of nitric oxide on the pathogenesis of irinotecan-induced intestinal mucositis: role of cytokines on inducible nitric oxide synthase activation

Wnt Pathway-Related Gene Expression in Inflammatory Bowel Disease

Tumor Necrosis Factor–Neuropeptide Y Cross Talk Regulates Inflammation, Epithelial Barrier Functions, and Colonic Motility

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