IL-1β Induces SOCS2 Expression in Human Dendritic Cells.

Muamera Sarajlic,Julia Vetter,Sara Michelini,Jutta Horejs-Hoeck,Theresa Neuper,Kim Tamara Föhrenbach Quiroz,Susanne Schaller

doi:10.3390/ijms20235931

Abstract

Dendritic cells (DCs) regulate immunity and inflammation and respond to various stimuli, including cytokines. IL-1β is a key cytokine in the course of both acute and chronic inflammatory responses, making it indispensable for protection of the host, but also linking it to several diseases. Thus, IL-1β signaling must be tightly regulated. As suppressor of cytokine signaling (SOCS) proteins effectively control immune responses, we investigated the role of SOCS2 in IL-1β-induced DC activation. Human monocyte-derived DCs were stimulated with IL-1β, and SOCS2 mRNA and protein levels were measured. DC activation was assessed by cytokine secretion and surface marker expression. For functional analysis, small interfering RNA (siRNA)-based SOCS2 silencing was performed. SOCS2 expression was also analyzed in a curated NCBI GEO dataset of myeloid leukemia patients. We found IL-1β to be a potent inducer of SOCS2 expression. By silencing SOCS2, we showed that SOCS2 specifically limits IL-1β-induced IL-8 secretion. Moreover, our analysis revealed that SOCS2 levels are significantly increased in patients with acute and chronic myeloid leukemia, two hematological malignancies where disease progression is closely linked to IL-1β. This study identifies SOCS2 as a novel IL-1β-inducible target gene and points toward a potential role of SOCS2 in IL-1β-mediated DC activation.

Highlights

The interleukin-1 (IL-1) family of cytokines plays a key role in immunity, as it is critically involved in triggering inflammatory responses such as secretion of various cytokines and chemokines as well as increased production of nitric oxide and adhesion molecules
To investigate whether suppressor of cytokine signaling 2 (SOCS2) might act as a negative feedback inhibitor of IL-1β signaling, we first monitored the ability of IL-1β to trigger SOCS2 expression
We investigated the dependence of SOCS2 expression on the concentration of IL-1β

Summary

Introduction

The interleukin-1 (IL-1) family of cytokines plays a key role in immunity, as it is critically involved in triggering inflammatory responses such as secretion of various cytokines and chemokines as well as increased production of nitric oxide and adhesion molecules. The subsequent interaction of MyD88 with IL-1R-associated kinases (IRAKs) [7,8] allows for binding of tumor necrosis factor-associated factor 6 (TRAF 6) [9], which in turn results in IL-1β-dependent activation of NF-κB [9], activator potein-1 (AP-1), extracellular signal-regulated kinases (ERK), p38 and other MAP kinases [10], c-Jun N-terminal kinase (JNK) and members of the interferon-regulatory factor (IRF) family [1] This potent immune response turns IL-1β into an effective trigger of acute phase responses; uncontrolled IL-1β signaling can drive chronic non-resolved inflammation, which is often associated with a wide variety of human pathologies, including autoimmunity and cancer [11,12]

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Results

Conclusion