title: Retinoic acid suppression of c-fos gene inhibits expression of tumor necrosis factor-alpha-induced monocyte chemoattractant JE/MCP-1 in clonal osteoblastic MC3T3-E1 cells.
abstract: Our previous study (Hanazawa, S., Takeshita, A., Amano, S., Semba, T., Nirazuka, T., Katoh, H., and Kitano, S. (1993) J. Biol. Chem. 268, 9526-9532) demonstrated that tumor necrosis factor-alpha (TNF-alpha) induces monocyte chemoattractant JE/MCP-1 expression via c-fos and c-jun genes following protein kinase C activation in osteoblastic MC3T3-E1 cells. In the present study, we examined the effect of retinoic acid (RA) on the cytokine-induced JE/MCP-1 expression in the cells. RA significantly inhibited the JE/MCP-1 gene expression by at least 6 h of pretreatment, and the inhibition was pretreatment time-dependent and occurred at the transcriptional level of the JE/MCP-1 gene expression. The RA-induced inhibition of the JE/MCP-1 gene product was also evidenced by both an assay involving immunoprecipitation with JE/MCP-1-specific antiserum and an assay for monocyte chemotaxis. Also, RA stimulated the gene expression of three different subclasses of RA receptor. RA pretreatment transcriptionally suppressed the expression of the c-fos gene but not that of the c-jun gene in TNF-alpha-treated cells. Antisense oligonucleotide to c-fos gene inhibited the cytokine-induced JE/MCP-1 gene expression in the cells. Furthermore, RA inhibited activator protein-1 binding to 12-O-tetradecanoylphorbol 13-acetate-response element (TRE) in the cells treated with TNF-alpha, suggesting that RA acts as a potent negative regulator for activator protein-1 binding activity to TRE in the osteoblastic cells.
authors.affiliation: Department of Oral Microbiology, Meikai University School of Dentistry, Saitama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hanazawa
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
authors.forename: S
authors.initials: S
authors.lastname: Kitano
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics*; D016207:Cytokines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin