SOCS3 Attenuates Dexamethasone-Induced M2 Polarization by Down-Regulation of GILZ Via ROS- and P38 MAPK-Dependent Pathways

Overview

Journal Immune Netw

Specialty Allergy & Immunology

Date 2022 Sep 9

PMID 36081527

Authors

Hana Jeong

Hyeyoung Yoon

Yerin Lee

Jun Tae Kim

Moses Yang

Gayoung Kim

Bom Jung

Seok Hee Park

Choong-Eun Lee

Affiliations

Soon will be listed here.

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, glucocorticoid-induced 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.

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