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

Fingerprint

T-cells
Osteoclasts
Interleukin-12
Gene expression
T-Lymphocytes
Gene Expression
Peptides
Interferons
Genes
Bone
Bone Marrow Cells
Real-Time Polymerase Chain Reaction
Messenger RNA
Jurkat Cells
Chromatin Immunoprecipitation
Neutralizing Antibodies
Luciferases
Interleukin-10
Chromatin
Assays

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

IL-12 stimulates the osteoclast inhibitory peptide-1 (OIP-1/hSca) gene expression in CD4+ T cells. / Shanmugarajan, Srinivasan; Kawanabe, Noriaki; Koide, Masanori; Tsuruga, Eichi; Arroyo, Jazmine E.; Key, Lyndon L.; Reddy, Sakamuri V.

In: Journal of Cellular Biochemistry, Vol. 107, No. 1, 01.05.2009, p. 104-111.

Research output: Contribution to journalArticle

Shanmugarajan, Srinivasan ; Kawanabe, Noriaki ; Koide, Masanori ; Tsuruga, Eichi ; Arroyo, Jazmine E. ; Key, Lyndon L. ; Reddy, Sakamuri V. / IL-12 stimulates the osteoclast inhibitory peptide-1 (OIP-1/hSca) gene expression in CD4+ T cells. In: Journal of Cellular Biochemistry. 2009 ; Vol. 107, No. 1. pp. 104-111.
@article{516d4e0dc29749ba9c4c0efe0e1dfc2b,
title = "IL-12 stimulates the osteoclast inhibitory peptide-1 (OIP-1/hSca) gene expression in CD4+ T cells",
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.",
keywords = "Bone marrow cells, Interferon-γ, Osteoclast inhibitory peptide-1, STAT, T cells",
author = "Srinivasan Shanmugarajan and Noriaki Kawanabe and Masanori Koide and Eichi Tsuruga and Arroyo, {Jazmine E.} and Key, {Lyndon L.} and Reddy, {Sakamuri V.}",
year = "2009",
month = "5",
day = "1",
doi = "10.1002/jcb.22104",
language = "English",
volume = "107",
pages = "104--111",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - IL-12 stimulates the osteoclast inhibitory peptide-1 (OIP-1/hSca) gene expression in CD4+ T cells

AU - Shanmugarajan, Srinivasan

AU - Kawanabe, Noriaki

AU - Koide, Masanori

AU - Tsuruga, Eichi

AU - Arroyo, Jazmine E.

AU - Key, Lyndon L.

AU - Reddy, Sakamuri V.

PY - 2009/5/1

Y1 - 2009/5/1

N2 - 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.

AB - 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.

KW - Bone marrow cells

KW - Interferon-γ

KW - Osteoclast inhibitory peptide-1

KW - STAT

KW - T cells

UR - http://www.scopus.com/inward/record.url?scp=66149185550&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66149185550&partnerID=8YFLogxK

U2 - 10.1002/jcb.22104

DO - 10.1002/jcb.22104

M3 - Article

VL - 107

SP - 104

EP - 111

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 1

ER -