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

ABSTRACT: Dendritic cells (DCs) regulate immunity and inflammation and respond to various stimuli, including cytokines. IL-1? 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-1? signaling must be tightly regulated. As suppressor of cytokine signaling (SOCS) proteins effectively control immune responses, we investigated the role of SOCS2 in IL-1?-induced DC activation. Human monocyte-derived DCs were stimulated with IL-1?, 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-1? to be a potent inducer of SOCS2 expression. By silencing SOCS2, we showed that SOCS2 specifically limits IL-1?-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-1?. This study identifies SOCS2 as a novel IL-1?-inducible target gene and points toward a potential role of SOCS2 in IL-1?-mediated DC activation.

SUBMITTER: Sarajlic M 

PROVIDER: S-EPMC6928683 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature