PT  - JOURNAL ARTICLE
AU  - Takigawa, Mutsumi
AU  - Iida, Manami
AU  - Nagase, Shotaro
AU  - Suzuki, Hidehiko
AU  - Watari, Akihiro
AU  - Tada, Minoru
AU  - Okada, Yoshiaki
AU  - Doi, Takefumi
AU  - Fukasawa, Masayoshi
AU  - Yagi, Kiyohito
AU  - Kunisawa, Jun
AU  - Kondoh, Masuo
TI  - Creation of a Claudin-2 Binder and Its Tight Junction–Modulating Activity in a Human Intestinal Model
AID  - 10.1124/jpet.117.242214
DP  - 2017 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 444--451
VI  - 363
IP  - 3
4099  - http://jpet.aspetjournals.org/content/363/3/444.short
4100  - http://jpet.aspetjournals.org/content/363/3/444.full
SO  - J Pharmacol Exp Ther2017 Dec 01; 363
AB  - 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-α (TNF-α), and cotreatment of cells with anti–TNF-α 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.