title: DHA protects against experimental colitis in IL-10-deficient mice associated with the modulation of intestinal epithelial barrier function.
abstract: A defect in the intestinal barrier is one of the characteristics of Crohn's disease (CD). The tight junction (TJ) changes and death of epithelial cells caused by intestinal inflammation play an important role in the development of CD. DHA, a long-chain PUFA, has been shown to be helpful in treating inflammatory bowel disease in experimental models by inhibiting the NF-κB pathway. The present study aimed at investigating the specific effect of DHA on the intestinal barrier function in IL-10-deficient mice. IL-10-deficient mice (IL-10(-/-)) at 16 weeks of age with established colitis were treated with DHA (i.g. 35.5 mg/kg per d) for 2 weeks. The severity of their colitis, levels of pro-inflammatory cytokines, epithelial gene expression, the distributions of TJ proteins (occludin and zona occludens (ZO)-1), and epithelial apoptosis in the proximal colon were measured at the end of the experiment. DHA treatment attenuated the established colitis and was associated with reduced infiltration of inflammatory cells in the colonic mucosa, lower mean histological scores and decreased levels of pro-inflammatory cytokines (IL-17, TNF-α and interferon-γ). Moreover, enhanced barrier function was observed in the DHA-treated mice that resulted from attenuated colonic permeability, rescued expression and corrected distributions of occludin and ZO-1. The results of the present study indicate that DHA therapy may ameliorate experimental colitis in IL-10(-/-) mice by improving the intestinal epithelial barrier function.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Peiliang
authors.initials: P
authors.lastname: Shi
authors.forename: Ye
authors.initials: Y
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Dong
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Wang
authors.forename: Lu-Gen
authors.initials: LG
authors.lastname: Zuo
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Gong
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Gu
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jie-Shou
authors.initials: JS
authors.lastname: Li
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics*; D020381:Interleukin-17 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D016328:NF-kappa B; D062793:Occludin; C568986:Ocln protein, mouse; C569043:Tjp1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D016753:Interleukin-10; D004281:Docosahexaenoic Acids; D007371:Interferon-gamma