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 language | English |
|---|---|
| Pages (from-to) | 104-111 |
| Number of pages | 8 |
| Journal | Journal of Cellular Biochemistry |
| Volume | 107 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 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
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 journal › Article
}
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 -