TY - JOUR
T1 - IL-1β Induces SOCS2 Expression in Human Dendritic Cells
AU - Sarajlic, Muamera
AU - Neuper, Theresa
AU - Föhrenbach Quiroz, Kim Tamara
AU - Michelini, Sara
AU - Vetter, Julia
AU - Schaller, Susanne
AU - Horejs-Hoeck, Jutta
N1 - Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - Dendritic cell
KW - IL-1β
KW - SOCS2
KW - Lymphocyte Activation/drug effects
KW - Signal Transduction
KW - Dendritic Cells/cytology
KW - Humans
KW - Cells, Cultured
KW - Interleukin-1beta/pharmacology
KW - Suppressor of Cytokine Signaling Proteins/genetics
KW - Monocytes/cytology
KW - Cell Differentiation
KW - Cytokines/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85075538234&partnerID=8YFLogxK
U2 - 10.3390/ijms20235931
DO - 10.3390/ijms20235931
M3 - Article
C2 - 31775389
SN - 1422-0067
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 23
M1 - 5931
ER -