Immune Netw.  2022 Aug;22(4):e33. 10.4110/in.2022.22.e33.

SOCS3 Attenuates DexamethasoneInduced M2 Polarization by DownRegulation of GILZ via ROS- and p38 MAPK-Dependent Pathways

• Jeong H
• Yoon H
• Lee Y
• Kim JT
• Yang M
• Kim G
• Jung B
• Park SH
• Lee CE

• KMID: 2536260
• DOI: http://doi.org/10.4110/in.2022.22.e33

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.

Keyword

Suppressors of cytokine signaling (SOCS)3; Type 2 macrophage (M2) polarization; Reactive oxygen species; Glucocorticoid-induced leucine zipper (GILZ); p38 MAPK