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

• Published in: Journal of international medical research Vol. 48; no. 6; p. 300060520926011
• Main Authors: Zhao, Caihong, Wang, Dong, Wu, Mengyao, Luo, Yuxin, Yang, Mingyue, Guo, Jinbo, Zhang, Hong, Zhang, Xiaolan
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.2020; Sage Publications Ltd; SAGE Publishing
• Subjects: Animals; Caco-2 Cells; China; Colitis - chemically induced; Colitis - metabolism; Colitis - pathology; Cytokines; Dextran Sulfate - pharmacology; Disease Models, Animal; Humans; Inflammatory bowel disease; Interleukin-9 - metabolism; Intestinal Mucosa - metabolism; Intestinal Mucosa - physiology; Ligands; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Necrosis; Pre-Clinical Research Report; Rodents; Tumor Necrosis Factor Ligand Superfamily Member 15 - metabolism; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; China; Inflammatory bowel disease; chronic colitis; intestinal mucosa barrier; dextran sodium sulfate; interleukin-9; tumor necrosis factor-like ligand 1A
• ISSN: 0300-0605; 1473-2300
• DOI: 10.1177/0300060520926011

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.