TGF-beta induces expression of monocyte chemoattractant JE/ monocyte chemoattractant protein 1 via transcriptional factor AP-1 induced by protein kinase in osteoblastic cells.
In this work, we demonstrate the signal-transducing mechanism of TGF-beta 1 for gene expression of monocyte chemoattractant JE/ monocyte chemoattractant protein 1 ( MCP-1) in clonal osteoblastic MC3T3-E1 cells. TGF-beta 1- induced JE/ MCP-1 gene expression in the cells was inhibited markedly by H-7 (1-(5-isoguinolinesulfonyl)-2-O-methylpiperazine-dihydrochloride) and staurosporine, potent inhibitors of protein kinase. TGF-beta 1- induced expression of both early proto-oncogenes c-fos and c-jun in the cells was also inhibited by H-7 and staurosporine. Antisense oligonucleotides to c-fos and c-jun genes inhibited significantly the cytokine- induced JE/ MCP-1 gene expression. Curcumin, a specific inhibitor of c-jun/ AP-1, inhibited the cytokine-induced c-jun gene expression in a dose-dependent manner, though the c-fos gene expression was not affected. TGF-beta 1 stimulated transcriptionally the JE/ MCP-1 gene expression, and this stimulation was inhibited significantly by curcumin. Curcumin-induced inhibition of the JE/ MCP-1 gene product was also evidenced by both an assay involving immunoprecipitation with antiserum specific for JE/ MCP-1 and an assay for monocyte chemotaxis. Curcumin markedly inhibited AP-1 binding activity to 12-tetradecanoyl phorbol-13-acetate-responsive element ( TRE) in the cytokine-treated cells. Furthermore, H-7 and staurosporine also inhibited the binding activity to TRE in the cells treated by the cytokine. These results demonstrate that TGF-beta 1 induces expression of monocyte chemoattractant JE/ MCP-1 via the transcriptional factor AP-1 induced by protein kinase in the osteoblastic cells.[1]References
- TGF-beta induces expression of monocyte chemoattractant JE/monocyte chemoattractant protein 1 via transcriptional factor AP-1 induced by protein kinase in osteoblastic cells. Takeshita, A., Chen, Y., Watanabe, A., Kitano, S., Hanazawa, S. J. Immunol. (1995) [Pubmed]
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