IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression

Biochem Biophys Res Commun. 2015 May 1;460(2):320-6. doi: 10.1016/j.bbrc.2015.03.033. Epub 2015 Mar 18.

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.

Keywords: Blimp-1; IL-33; IRF-8; Osteoclastogenesis.

MeSH terms

  • 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*

Substances

  • DNA Primers
  • Il33 protein, mouse
  • Interferon Regulatory Factors
  • Interleukin-33
  • Interleukins
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Prdm1 protein, mouse
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Transcription Factors
  • interferon regulatory factor-8
  • Positive Regulatory Domain I-Binding Factor 1