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Oleoylethanolamide Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats.

ABSTRACT: Oleoylethanolamide (OEA) is an endogenous fatty acid ethanolamide known for its anti-inflammatory effects and its influence on gut microbiota composition; however, the effects of OEA in inflammatory bowel disease (IBD) remain unknown. During in vitro experiments, OEA downregulated the expression of tumor necrosis factor (TNF)-? and reduced phosphorylation of inhibitor of kappa (I?) B? induced by lipopolysaccharide in human embryonic kidney cells. Moreover, OEA downregulated the expression of interleukin (IL)-8 and IL-1? and inhibited the phosphorylation of I?B? and p65 induced by TNF-? in human enterocytes (Caco-2). The effect of OEA in reducing the expression of IL-8 was blocked by the peroxisome proliferator-activated receptor (PPAR)-? antagonist. During in vivo experiments on rats, colitis was induced by the oral administration of 8% dextran sulfate sodium from day 0 through day 5, and OEA (20 mg/kg) was intraperitoneally injected once a day from day 0 for 6 days. OEA administration significantly ameliorated the reduction in body weight, the increase in disease activity index score, and the shortening of colon length. In rectums, OEA administration reduced the infiltration of macrophages and neutrophils and tended to reduce the histological score and the expression of inflammatory cytokines. Administration of OEA produced significant improvement in a colitis model, possibly by inhibiting the nuclear factor kappa B signaling pathway through PPAR-? receptors. OEA could be a potential new treatment for IBD.

SUBMITTER: Otagiri S

PROVIDER: S-EPMC7457075 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Oleoylethanolamide Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats.

Otagiri Shinsuke S Ohnishi Shunsuke S Ohara Masatsugu M Fu Qingjie Q Yamamoto Koji K Yamamoto Keiko K Katsurada Takehiko T Sakamoto Naoya N

Frontiers in pharmacology 20200814

Oleoylethanolamide (OEA) is an endogenous fatty acid ethanolamide known for its anti-inflammatory effects and its influence on gut microbiota composition; however, the effects of OEA in inflammatory bowel disease (IBD) remain unknown. During <i>in vitro</i> experiments, OEA downregulated the expression of tumor necrosis factor (TNF)-α and reduced phosphorylation of inhibitor of kappa (Iκ) Bα induced by lipopolysaccharide in human embryonic kidney cells. Moreover, OEA downregulated the expression ...[more]

PMID: 32922296

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Project description:Alterations in the intestinal lymphatic network are pathological processes as related to inflammatory bowel disease (IBD). In this study, we demonstrated that reduction in inflammation-induced lymphangiogenesis ameliorates experimental acute colitis. A soluble and stable angiopoietin-1 (Ang1) variant, COMP-Ang1, possesses anti-inflammatory and angiogenic effects. We investigated the effects of COMP-Ang1 on an experimental colonic inflammation model. Experimental colitis was induced in mice by administering 3% dextran sulfate sodium (DSS) via drinking water. We determined body weight, disease activity indices, histopathological scores, lymphatic density, anti-ER-HR3 staining, and the expression of members of the vascular endothelial growth factor (VEGF) family and various inflammatory cytokines in the mice. The density of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and VEGFR-3-positive lymphatic vessels increased in mice with DSS-induced colitis. We observed that COMP-Ang1-treated mice showed less weight loss, fewer clinical signs of colitis, and longer colons than Ade-DSS-treated mice. COMP-Ang1 also significantly reduced the density of LYVE-1-positive lymphatic vessels and the disruption of colonic architecture that is normally associated with colitis and repressed the immunoregulatory response. Further, COMP-Ang1 treatment reduced both M1 and M2 macrophage infiltration into the inflamed colon, which involved inhibition of VEGF-C and D expression. Thus, COMP-Ang1, which acts by reducing inflammation-induced lymphangiogenesis, may be used as a novel therapeutic for the treatment of IBD and other inflammatory diseases.Key messagesCOMP-Ang1 decreases inflammatory-induced lymphangiogenesis in experimental acute colitis. COMP-Ang1 improves the symptom of DSS-induced inflammatory response. COMP-Ang1 reduces the expression of pro-inflammatory cytokines in inflamed colon. COMP-Ang1 reduces the expression of VEGFs in inflamed colon. COMP-Ang1 prevents infiltration of macrophages in a DSS-induced colitis model.

Dataset Information

Oleoylethanolamide Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats.

Publications

Oleoylethanolamide Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats.

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