RRC ID 36931
Author Kiyomiya H, Ariyoshi W, Okinaga T, Kaneuji T, Mitsugi S, Sakurai T, Habu M, Yoshioka I, Tominaga K, Nishihara T.
Title IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression.
Journal Biochem Biophys Res Commun
Abstract Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression.
Volume 460(2)
Pages 320-6
Published 2015-5-1
DOI 10.1016/j.bbrc.2015.03.033
PII S0006-291X(15)00468-4
PMID 25795135
MeSH Animals Base Sequence Cell Line Cells, Cultured DNA Primers Female Interferon Regulatory Factors / genetics Interferon Regulatory Factors / metabolism* Interleukin-33 Interleukins / physiology* Male Mice NFATC Transcription Factors / genetics NFATC Transcription Factors / metabolism Osteoclasts / cytology* Positive Regulatory Domain I-Binding Factor 1 RANK Ligand / antagonists & inhibitors* RANK Ligand / physiology Real-Time Polymerase Chain Reaction Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism*
IF 2.705
Times Cited 18
Human and Animal Cells