n-3 polyunsaturated fatty acids prevent disruption of epithelial barrier function induced by proinflammatory cytokines.
Defects in tight junction barrier have been considered as an important etiologic factor of Crohn's disease. n-3 polyunsaturated fatty acids (PUFAs) exert beneficial effects on inflammatory bowel disorders. However, the mechanisms remain unknown. We found that docosahexaenoic acid (DHA, 22:6 n-3) and eicosapentaenoic acid (EPA, 20:5 n-3) changed lipid environment in membrane microdomains of tight junction in vitro. n-3 PUFAs treatment effectively prevented the redistribution of occludin and ZO-1 and distortion of TJ morphology, reduced transepithelial electrical resistance induced by IFN-gamma and TNF-alpha. We also observed dramatic reorganization of TJ proteins in epithelial lateral membrane following treatment with these cytokines. Our findings for first time indicate that n-3 PUFAs play an important role in proinflammatory cytokines-induced permeability defects and epithelial barrier dysfunction by modifying lipid environment in membrane microdomains of tight junction.
Li
Qiurong
Q
Institute of General Surgery, Jinling Hospital, No 305 East Zhongshan Road, Nanjing 210002, China.
Zhang
Qiang
Q
Wang
Meng
M
Zhao
Sumin
S
Xu
Guowang
G
Li
Jieshou
J
D002463:Cell Membrane Permeability; D016207:Cytokines / Q000494:pharmacology*; D004848:Epithelium / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D021962:Membrane Microdomains / Q000737:chemistry*; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D019108:Tight Junctions / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein
D016207:Cytokines; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D007371:Interferon-gamma