RT Journal Article
SR Electronic
T1 Creation of a Claudin-2 Binder and Its Tight Junction–Modulating Activity in a Human Intestinal Model
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 444
OP 451
DO 10.1124/jpet.117.242214
VO 363
IS 3
A1 Takigawa, Mutsumi
A1 Iida, Manami
A1 Nagase, Shotaro
A1 Suzuki, Hidehiko
A1 Watari, Akihiro
A1 Tada, Minoru
A1 Okada, Yoshiaki
A1 Doi, Takefumi
A1 Fukasawa, Masayoshi
A1 Yagi, Kiyohito
A1 Kunisawa, Jun
A1 Kondoh, Masuo
YR 2017
UL http://jpet.aspetjournals.org/content/363/3/444.abstract
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.