Suppressor of cytokine signaling 3 inhibits LPS-induced IL-6 expression in osteoblasts by suppressing CCAAT/enhancer-binding protein

Chunguang Yan, Jay Cao, Min Wu, Wei Zhang, Tao Jiang, Akihiko Yoshimura, Hongwei Gao

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Suppressor of cytokine signaling 3 (SOCS3) is an important intracellular protein that inhibits cytokine signaling in numerous cell types and has been implicated in several inflammatory diseases. However, the expression and function of SOCS3 in osteoblasts are not known. In this study, we demonstrated that SOCS3 expression was transiently induced by LPS in osteoblasts, and apparently contributed to the inhibition of IL-6 induction by LPS treatment. We found that tyrosine 204 of the SOCS box, the SH2 domain, and the N-terminal kinase inhibitory region (KIR) of SOCS3 were all involved in its IL-6 inhibition. Furthermore, we demonstrated that CCAAT/enhancerbinding protein (C/EBP) β was activated by LPS (increased DNA binding activity), and played a key role in LPS-induced IL-6 expression in osteoblasts. We further provided the evidence that SOCS3 functioned as a negative regulator for LPS response in osteoblasts by suppressing C/EBPβ DNA binding activity. In addition, tyrosine 204 of the SOCS box, the SH2 domain, and the N-terminal kinase inhibitory region (KIR) of SOCS3 were all required for its C/EBPβ inhibition. These findings suggest that SOCS3 by interfering with C/EBPβ activation may have an important regulatory role during bone-associated inflammatory responses.

Original languageEnglish
Pages (from-to)37227-37239
Number of pages13
JournalJournal of Biological Chemistry
Volume285
Issue number48
DOIs
Publication statusPublished - 2010 Nov 26

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CCAAT-Enhancer-Binding Proteins
Osteoblasts
Interleukin-6
Cytokines
src Homology Domains
Tyrosine
Proteins
Phosphotransferases
DNA-Binding Proteins
Bone
Chemical activation
Bone and Bones
DNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Suppressor of cytokine signaling 3 inhibits LPS-induced IL-6 expression in osteoblasts by suppressing CCAAT/enhancer-binding protein. / Yan, Chunguang; Cao, Jay; Wu, Min; Zhang, Wei; Jiang, Tao; Yoshimura, Akihiko; Gao, Hongwei.

In: Journal of Biological Chemistry, Vol. 285, No. 48, 26.11.2010, p. 37227-37239.

Research output: Contribution to journalArticle

Yan, Chunguang ; Cao, Jay ; Wu, Min ; Zhang, Wei ; Jiang, Tao ; Yoshimura, Akihiko ; Gao, Hongwei. / Suppressor of cytokine signaling 3 inhibits LPS-induced IL-6 expression in osteoblasts by suppressing CCAAT/enhancer-binding protein. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 48. pp. 37227-37239.
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