SOCS3 Attenuates DexamethasoneInduced M2 Polarization by DownRegulation of GILZ via ROS- and p38 MAPK-Dependent Pathways
- Author:
Hana JEONG
1
;
Hyeyoung YOON
;
Yerin LEE
;
Jun Tae KIM
;
Moses YANG
;
Gayoung KIM
;
Bom JUNG
;
Seok Hee PARK
;
Choong-Eun LEE
Author Information
- Publication Type:Original Article
- From:Immune Network 2022;22(4):e33-
- CountryRepublic of Korea
- Language:English
- Abstract: Suppressors of cytokine signaling (SOCS) have emerged as potential regulators of macrophage function. We have investigated mechanisms of SOCS3 action on type 2 macrophage (M2) differentiation induced by glucocorticoid using human monocytic cell lines and mouse bone marrow-derived macrophages. Treatment of THP1 monocytic cells with dexamethasone (Dex) induced ROS generation and M2 polarization promoting IL-10 and TGF-β production, while suppressing IL-1β, TNF-α and IL-6 production. SOCS3 over-expression reduced, whereas SOCS3 ablation enhanced IL-10 and TGF-β induction with concomitant regulation of ROS. As a mediator of M2 differentiation, glucocorticoidinduced leucine zipper (GILZ) was down-regulated by SOCS3 and up-regulated by shSOCS3. The induction of GILZ and IL-10 by Dex was dependent on ROS and p38 MAPK activity. Importantly, GILZ ablation led to the inhibition of ROS generation and anti-inflammatory cytokine induction by Dex. Moreover, GILZ knock-down negated the up-regulation of IL-10 production induced by shSOCS3 transduction. Our data suggest that SOCS3 targets ROS- and p38-dependent GILZ expression to suppress Dex-induced M2 polarization.
