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KMID : 0923620220220040033
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Immune Network
2022 Volume.22 No. 4 p.33 ~ p.33
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SOCS3 Attenuates Dexamethasone-Induced M2 Polarization by Down-Regulation of GILZ via ROS- and p38 MAPK-Dependent Pathways
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Jeong Ha-Na
Yoon Hye-Young
Lee Ye-Rin
Kim Jun-Tae
Yang Moses
Kim Ga-Young
Jung Bom
Park Seok-Hee
Lee Choong-Eun
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Abstract
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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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KEYWORD
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Suppressors of cytokine signaling (SOCS)3, Type 2 macrophage (M2) polarization, Reactive oxygen species, Glucocorticoid-induced leucine zipper (GILZ), p38 MAPK
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