The leukotriene B4 receptor BLT2 protects barrier function via actin polymerization with phosphorylation of myosin phosphatase target subunit 1 in human keratinocytes

Takahito Chiba, Takeshi Nakahara, Akiko Hashimoto-Hachiya, Takehiko Yokomizo, Hiroshi Uchi, Masutaka Furue

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)532-536
Number of pages5
JournalExperimental Dermatology
Volume25
Issue number7
DOIs
Publication statusPublished - Jul 1 2016

Fingerprint

Leukotriene B4 Receptors
Myosin-Light-Chain Phosphatase
Phosphorylation
Keratinocytes
Polymerization
Actins
Permeability
Acoustic impedance
Dextrans
Calcium
Electric Impedance
Leukotriene B4
Tight Junctions
G-Protein-Coupled Receptors
Skin Diseases
Ligation
12-hydroxy-5,8,10-heptadecatrienoic acid
Assays
Skin
Adhesion

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

The leukotriene B4 receptor BLT2 protects barrier function via actin polymerization with phosphorylation of myosin phosphatase target subunit 1 in human keratinocytes. / Chiba, Takahito; Nakahara, Takeshi; Hashimoto-Hachiya, Akiko; Yokomizo, Takehiko; Uchi, Hiroshi; Furue, Masutaka.

In: Experimental Dermatology, Vol. 25, No. 7, 01.07.2016, p. 532-536.

Research output: Contribution to journalArticle

@article{aafef1afe56d4c858748ebcae6bf977a,
title = "The leukotriene B4 receptor BLT2 protects barrier function via actin polymerization with phosphorylation of myosin phosphatase target subunit 1 in human keratinocytes",
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.",
author = "Takahito Chiba and Takeshi Nakahara and Akiko Hashimoto-Hachiya and Takehiko Yokomizo and Hiroshi Uchi and Masutaka Furue",
year = "2016",
month = "7",
day = "1",
doi = "10.1111/exd.12976",
language = "English",
volume = "25",
pages = "532--536",
journal = "Experimental Dermatology",
issn = "0906-6705",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - The leukotriene B4 receptor BLT2 protects barrier function via actin polymerization with phosphorylation of myosin phosphatase target subunit 1 in human keratinocytes

AU - Chiba, Takahito

AU - Nakahara, Takeshi

AU - Hashimoto-Hachiya, Akiko

AU - Yokomizo, Takehiko

AU - Uchi, Hiroshi

AU - Furue, Masutaka

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84977110472&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84977110472&partnerID=8YFLogxK

U2 - 10.1111/exd.12976

DO - 10.1111/exd.12976

M3 - Article

C2 - 26896822

AN - SCOPUS:84977110472

VL - 25

SP - 532

EP - 536

JO - Experimental Dermatology

JF - Experimental Dermatology

SN - 0906-6705

IS - 7

ER -