IL-12 stimulates the osteoclast inhibitory peptide-1 (OIP-1/hSca) gene expression in CD4+ T cells

Srinivasan Shanmugarajan, Noriaki Kawanabe, Masanori Koide, Eichi Tsuruga, Jazmine E. Arroyo, Lyndon L. Key, Sakamuri V. Reddy

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Immune cell products such as interferon (IFN)-γ and interleukin (IL)-12 are potent inhibitors of osteoclast formation. We previously characterized the human osteoclast inhibitory peptide-1 (OIP-1/hSca), a Ly-6 gene family member and showed IFN-γ modulation of OIP-1 expression in bone marrow cells. Whether, IL-12 regulates OIP-1 expression in the bone microenvironment is unclear. Real-time PCR analysis revealed that IL-12 treatment significantly enhanced OIP-1 mRNA expression in human bone marrow mononuclear cells. Because IL-12 induces IFN-γ production by T cells, we tested whether IFN-γ participates in IL-12 stimulation of OIP-1 gene expression in these cells. IL-12 treatment in the presence of IFN-γ neutralizing antibody significantly increased OIP-1 mRNA expression, suggesting that IL-12 directly regulates OIP-1 gene expression. Interestingly, real-time PCR analysis demonstrated that IL-12 induces OIP-1 expression (3.2-fold) in CD4+ T cells; however, there was no significant change in CD8+ T cells. Also, IL-12 (10 ng/ml) treatment of Jurkat cells transfected with OIP-1 gene (-1 to -1,988 bp) promoter-luciferase reporter plasmid demonstrated a 5-fold and 2.7-fold increase in OIP-1 gene promoter activity in the presence and absence of antibody against IFN-γ, respectively. We showed that STAT-1,3 inhibitors treatment significantly decreased IL-12 stimulated OIP-1 promoter activity. Chromatin immunoprecipitation (ChIP) assay confirmed STAT-3, but not STAT-1 binding to the OIP-1 gene promoter in response to IL-12 stimulation. These results suggest that IL-12 stimulates the OIP-1 gene expression through STAT-3 activation in CD4+ T cells.

Original languageEnglish
Pages (from-to)104-111
Number of pages8
JournalJournal of Cellular Biochemistry
Volume107
Issue number1
DOIs
Publication statusPublished - May 1 2009

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Keywords

  • Bone marrow cells
  • Interferon-γ
  • Osteoclast inhibitory peptide-1
  • STAT
  • T cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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