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- Title
The leukotriene B<sub>4</sub> receptor BLT2 protects barrier function via actin polymerization with phosphorylation of myosin phosphatase target subunit 1 in human keratinocytes.
- Authors
Chiba, Takahito; Nakahara, Takeshi; Hashimoto ‐ Hachiya, Akiko; Yokomizo, Takehiko; Uchi, Hiroshi; Furue, Masutaka
- Abstract
Leukotriene B4 ( LTB4) receptor type 2 ( BLT2) 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 LTB4. Recently, 12- HHT has been shown to have a protective effect on the epidermal barrier in human keratinocytes or transfectant cells overexpressing BLT2. Because the protective activity of BLT2 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 BLT2 protects permeability barrier function by enhancing cell-cell contact, even under low-calcium conditions, and indicate that a BLT2 agonist could be a novel therapeutic target for barrier-disrupted skin diseases.
- Subjects
SKIN diseases; LEUKOTRIENES; POLYMERIZATION; ACTIN; MYOSIN; KERATINOCYTE differentiation; THERAPEUTICS
- Publication
Experimental Dermatology, 2016, Vol 25, Issue 7, p532
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/exd.12976