Tumor necrosis factor ligand-related molecule 1A affects the intestinal mucosal barrier function by promoting Th9/interleukin-9 expression

Objectives To investigate the effect of tumor necrosis factor ligand-related molecule 1A (TL1A) on the intestinal mucosal barrier in mice with chronic colitis. Methods Male TL1A-overexpressing transgenic mice and male C57BL/6 wild-type mice were used to establish a dextran sodium sulfate (DSS)-induc...

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Veröffentlicht in:Journal of international medical research 2020-06, Vol.48 (6), p.300060520926011
Hauptverfasser: Zhao, Caihong, Wang, Dong, Wu, Mengyao, Luo, Yuxin, Yang, Mingyue, Guo, Jinbo, Zhang, Hong, Zhang, Xiaolan
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Sprache:eng
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Zusammenfassung:Objectives To investigate the effect of tumor necrosis factor ligand-related molecule 1A (TL1A) on the intestinal mucosal barrier in mice with chronic colitis. Methods Male TL1A-overexpressing transgenic mice and male C57BL/6 wild-type mice were used to establish a dextran sodium sulfate (DSS)-induced colitis model. The expression of occludin and claudin-1 was observed. Bacterial distribution in the intestinal mucosa and Th9/interleukin (IL)-9 expression were detected. In vitro co-culture systems of naive CD4+ T cells and Caco-2 cells were established and TL1A was added. Changes in transepithelial electrical resistance and IL-9 expression were measured. CD4+IL-9 cells were detected by flow cytometry. Results DSS mice showed a significant down-regulation of occludin and claudin-1 compared with controls. Expression levels of occludin, zonulin-1, and claudin-1 in the Caco-2+TGF-β+IL-4+TL1A group were significantly lower than in the Caco-2+TGF-β+IL-4 group. Bacterial distribution was clearly disordered in the DSS group. Transmembrane resistance of the Caco-2+TGF-β+IL-4+TL1A group was significantly lower and IL-9 expression significantly higher than in the Caco-2+TGF-β+IL-4 group. Conclusions TL1A overexpression promotes destruction of the intestinal mucosal barrier in mice with chronic colitis. The underlying mechanism may be associated with the promoting role of TL1A in Th9/IL-9 expression, which further destroys the mucosal barrier.
ISSN:0300-0605
1473-2300
DOI:10.1177/0300060520926011