Page 44 - M. Immunology

[M. Immunology-28]

Mechanism of SOCS1 action in the promotion of

glucocorticoid-induced M2 polarization: Role of p38-GILZ

and HIF-1 as a target of SOCS1

Hana Jeong¹, Choong-Eun Lee¹˙*

¹Department of Biological Science, Sungkyunkwan University, Suwon 440746, Korea

Macrophages are critical role players in the host defense, exhibiting pro-inflammatory (M1) and anti-inflammatory
(M2) functions in different phases of infection to maintain immune homeostasis. As a part of our study on the
regulatory effects of suppressors of cytokine signaling (SOCS) in M1 vs M2 differentiation, we have investigated the

mechanism of SOCS1 action on M2 typeα macrophage polarization induced by glucocorticoid (GC) using monocytic
cells transduced with SOCS1 or shSOCS1. Dex, a synthetic GC induced ROS generation, p38/MKP1 activity, and GILZ

leading to IL-10 production and other M2 markers by 24-48 h. SOCS1 and shSOCS1 reciprocally affected GC-
induced M2 polarization as shown by up-regulation of IL-10 production with p38 and GILZ by SOCS1 and down-

regulation by shSOCS1. As M2 polarization involves the metabolic switch from M1 to M2, the role of an M1 type
metabolic regulator HIF-1 was examined as a potential target of SOCS1. In SOCS1-transduced cells HIF-1α levels

were down-regulated with increased ubiquitination, whereas forced up-regulation of HIF-1α attenuated the increase
of IL-10 induced by SOCS1. The data suggest that SOCS1 promotes GC-induced M2 polarization via p38-dependent

GILZ up-regulation and HIF-1α down-regulation.<Supported by KRF # 2018R1A2B6002201>