PT - JOURNAL ARTICLE AU - Misaki Nakajima AU - Shotaro Nagase AU - Manami Iida AU - Shuji Takeda AU - Mayo Yamashita AU - Akihiro Watari AU - Yoshitaka Shirasago AU - Masayoshi Fukasawa AU - Hiroyuki Takeda AU - Tatsuya Sawasaki AU - Kiyohito Yagi AU - Masuo Kondoh TI - Claudin-1 Binder Enhances Epidermal Permeability in a Human Keratinocyte Model AID - 10.1124/jpet.115.225391 DP - 2015 Sep 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 440--447 VI - 354 IP - 3 4099 - http://jpet.aspetjournals.org/content/354/3/440.short 4100 - http://jpet.aspetjournals.org/content/354/3/440.full SO - J Pharmacol Exp Ther2015 Sep 01; 354 AB - Tight junctions (TJs) are complex biochemical structures that seal the intercellular space and prevent the free movement of solutes across epithelial cell sheets. Modulating the TJ seal is a promising option for increasing the transdermal absorption of drugs. Within TJs, the binding of the claudin (CLDN) family of tetratransmembrane proteins through cis- and trans-interactions is an integral part of seal formation. Because epidermal TJs contain CLDN-1 and CLDN-4, a binder for these CLDNs may be a useful modulator of the permeability of the epidermal barrier. Here, we investigated whether m19, which can bind to CLDN-1/-4 (also CLDN-2/-5), modulates the integrity of epidermal TJs and the permeability of cell sheets to solutes. Treatment of normal human epidermal keratinocytes (NHEKs) with the CLDN binder reduced the integrity of TJs. A CLDN-1–specific binder (a monoclonal antibody, clone 7A5) also weakened the TJ seal in NHEKs. Although m19 attenuated the TJ barrier in human intestinal epithelial cells (Caco-2), 7A5 did not. Treatment of NHEKs with 7A5 enhanced permeation of a paracellular permeation marker. These findings indicate that CLDN-1 is a potential target for modulating the permeability of the epidermis, and that our CLDN-1 binder is a promising candidate molecule for development as a dermal absorption enhancer.