Berberine attenuates pro-inflammatory cytokine-induced tight junction disruption in an in vitro model of intestinal epithelial cells.
Maintenance of the mucosal barrier is a critical function of intestinal epithelial tight junction. Berberine is one of the main constituents of Coptidis rhizoma, which has been used for patients with gastrointestinal disorders for a long time. This study aimed to determine whether berberine could alleviate pro-inflammatory cytokine-induced intestinal epithelial tight junction damage. Caco-2 monolayers were treated with tumor necrosis factor-alpha and interferon-gamma to induce barrier dysfunction. The protective effect of berberine on tight junctions was analyzed by measuring the trans-epithelial electrical resistance (TEER). Transmission electron microscopy was used to observe the morphology of tight junction, and subcellular localization of tight junction proteins was investigated by immunofluorescence microscopy and Western blot. Berberine significantly prevented pro-inflammatory cytokines induced decrease in TEER. The distortion of tight junction morphology and redistribution of tight junction protein occludin was also prevented by berberine treatment. Western blot analysis demonstrated that berberine inhibit the dislocation of occludin from raft fractions to non-raft fractions in membrane microdomains of tight junctions. We concluded that berberine can ameliorate pro-inflammatory cytokines induced intestinal epithelia tight junction damage in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states.
Research Institute of General Surgery, Nanjing JingLing Hospital, Second Military Medical University, Nanjing, China.
Ning
N
Li
Lili
L
Gu
Linlin
L
Qu
Jianfeng
J
Gong
Qiurong
Q
Li
Weiming
W
Zhu
Jieshou
J
Li
D001599:Berberine / Q000494:pharmacology*; D018938:Caco-2 Cells; D016207:Cytokines / Q000494:pharmacology*; D003896:Desmosomes / Q000187:drug effects / Q000648:ultrastructure; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology*; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010539:Permeability / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D018836:Inflammation Mediators; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D014409:Tumor Necrosis Factor-alpha; C106354:flotillins; D001599:Berberine; D007371:Interferon-gamma