期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 363, 期 3, 页码 444-451出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.117.242214
关键词
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资金
- Health and Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan
- Japan Agency for Medical Research and Development
- Ministry of Education, Culture, Sports, Science, and Technology of (MEXT) of Japan/Japan Society for the Promotion of Science KAKENHI [16H01373]
- Adaptable and Seamless Technology Transfer Program through Target-driven R&D, Japan Science and Technology Agency
- Platform for Drug Discovery, Informatics, and Structural Life Science from MEXT of Japan
- Takeda Science Foundation
- Advanced Research for Medical Products Mining Program of the National Institute of Biomedical Innovation
- Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries, and Food Industry
- Nipponham Foundation for the Future of Food
- Grants-in-Aid for Scientific Research [16K08370, 26293111, 16H01373, 17K19487] Funding Source: KAKEN
Disruption of the gastrointestinal epithelial barrier is a hallmark of chronic inflammatory bowel diseases (IBDs). The transmembrane protein claudin 2 (CLDN2) is a component of epithelial tight junctions (TJs). In the intestines of patients with IBDs, the expression of the pore-forming TJ protein CLDN2 is upregulated. Although CLDN2 is involved in these leaky barriers, whether it can be a target to enhance TJ integrity is unknown because a CLDN2-specific inhibitor has not been developed. Here, we used DNA immunization to generate a monoclonal antibody (mAb) that recognized an extracellular loop of CLDN2. Treatment of epithelial cell monolayers with the mAb increased barrier integrity. In addition, the anti-CLDN2 mAb attenuated the decrease in TJ integrity induced by the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), and cotreatment of cells with anti-TNF-alpha mAb and anti-CLDN2 mAb showed additive attenuating effects. These findings indicate that CLDN2 may be a target for enhancing TJ integrity, and CLDN2 binder may be an enhancer of mucosal barrier integrity and a potential therapeutic option for IBDs.
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