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 language | English |
|---|---|
| Pages (from-to) | 532-536 |
| Number of pages | 5 |
| Journal | Experimental Dermatology |
| Volume | 25 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 1 2016 |
Fingerprint
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 journal › Article
}
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 -