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The leukotriene B 4 receptor BLT 2 protects barrier function via actin polymerization with phosphorylation of myosin phosphatase target subunit 1 in human keratinocytes
Author(s) -
Chiba Takahito,
Nakahara Takeshi,
HashimotoHachiya Akiko,
Yokomizo Takehiko,
Uchi Hiroshi,
Furue Masutaka
Publication year - 2016
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12976
Subject(s) - barrier function , chemistry , rhoa , myosin light chain kinase , biophysics , microbiology and biotechnology , phosphorylation , biochemistry , biology , signal transduction
Leukotriene B 4 ( LTB 4 ) receptor type 2 ( BLT 2) is a novel G‐protein‐coupled receptor, which selectively binds to 12(S)‐hydroxyheptadeca‐5Z,8E,10E‐trienoic acid (12‐ HHT ) with stronger affinity than to LTB 4 . Recently, 12‐ HHT has been shown to have a protective effect on the epidermal barrier in human keratinocytes or transfectant cells overexpressing BLT 2. Because the protective activity of BLT 2 in high‐calcium conditions, which occurs in well‐differentiated cells, is exerted through increasing the integrity of tight junctions, we investigated the effects of 12‐ HHT on the barrier function of human keratinocytes in low‐calcium conditions that mimic the basal layer; to our knowledge, this has not been reported previously. After stimulation with or without 12‐ HHT , barrier function was measured using transepithelial electrical resistance ( TER ) and dextran permeability assay. Expression levels of adhesion molecules and actin polymerization were also evaluated. Treatment with 12‐ HHT increased TER , along with decreased epidermal permeability of dextran in human keratinocytes. Furthermore, 12‐ HHT induced actin polymerization with phosphorylation of myosin phosphatase target subunit 1. These results suggest that the ligation of BLT 2 protects permeability barrier function by enhancing cell–cell contact, even under low‐calcium conditions, and indicate that a BLT 2 agonist could be a novel therapeutic target for barrier‐disrupted skin diseases.