| RRC ID |
68430
|
| 著者 |
Okamoto Y, Kitakaze K, Takenouchi Y, Yamamoto S, Ishimaru H, Tsuboi K.
|
| タイトル |
Sphingosine 1-phosphate receptor type 2 positively regulates interleukin (IL)-4/IL-13-induced STAT6 phosphorylation.
|
| ジャーナル |
Cell Signal
|
| Abstract |
Previous reports have demonstrated that sphingosine 1-phosphate receptor type 2 (S1P2) is involved in the activation of signal transducer and activator of transcription (STAT) 6. Additionally, the major signaling pathway of S1P2 is the Rho-Rho kinase pathway. In this study, we examined the role of S1P2 in STAT6 activation in a macrophage (Mφ) model using THP-1 cells differentiated with phorbol 12-myristate 13-acetate (PMA). We established S1P2knockout THP-1 cells using the CRISPR-Cas9 gene editing system. The PMA-treated S1P2knockout THP-1 Mφs showed decreases in IL-4/IL-13-induced phosphorylation of Janus-activated kinase (JAK) 1, JAK2, and STAT6 as well as mRNA expression of the M2 marker ARG1 compared with wild-type THP-1 Mφs. Pretreatment of PMA-treated THP-1 Mφs with the S1P2 antagonist JTE-013, the Rho inhibitor Rhosin or the Rho kinase inhibitor Y27632 inhibited the IL-4/IL-13-induced increase in STAT6 phosphorylation. The expressions of suppressor of cytokine signaling 3 in the S1P2knockout THP-1 Mφs were higher than those in wild-type THP-1 Mφs. In addition, the protein tyrosine phosphatase inhibitor vanadate enhanced IL-4-induced STAT6 phosphorylation in the S1P2knockout THP-1 Mφs, suggesting that S1P2-Rho-Rho kinase inhibited the negative regulation of STAT6. These results suggest that the S1P2-Rho-Rho kinase pathway is necessary for full activation of STAT6 by IL-4/IL-13 in Mφs.
|
| 巻・号 |
88
|
| ページ |
110156
|
| 公開日 |
2021-12-1
|
| DOI |
10.1016/j.cellsig.2021.110156
|
| PII |
S0898-6568(21)00245-X
|
| PMID |
34592416
|
| MeSH |
Interleukin-13* / metabolism
Phosphorylation
STAT6 Transcription Factor / metabolism
Signal Transduction*
Sphingosine / metabolism
Sphingosine / pharmacology
Sphingosine-1-Phosphate Receptors
|
| IF |
3.968
|
| リソース情報 |
| ヒト・動物細胞 |
THP-1(RCB3686) |
