Tumor necrosis factor-alpha induces expression of monocyte chemoattractant JE via fos and jun genes in clonal osteoblastic MC3T3-E1 cells.
The mechanism by which circulating monocytes are attracted to sites of bone remodeling is unknown. We now report that tumor necrosis factor-alpha (TNF-alpha), a potent osteotrophic cytokine, was stimulatory for expression of the monocyte chemoattractant JE gene in osteoblastic MC3T3-E1 cells. TNF-alpha stimulated this JE gene expression transcriptionally. The presence of JE gene product in conditioned medium of the cytokine-treated cells was evidenced by an immunoprecipitation assay with antiserum specific for JE/MCP-1. The stimulated JE gene expression was markedly inhibited by H-7, a potent inhibitor of protein kinase C. Phorbol 12-myristate 13-acetate induced the JE gene expression, and the cytokine-induced JE gene expression was down-regulated by the phorbol ester pretreatment. TNF-alpha induced expression of both early protooncogenes, c-fos and c-jun, in the cells. Antisense oligonucleotides to these oncogenes significantly inhibited the cytokine-induced monocyte chemotactic activity. Furthermore, curcumin, a specific inhibitor of c-jun/AP-1, markedly inhibited JE gene expression and monocyte chemotactic activity induced by the cytokine. These results suggest that TNF-alpha may contribute to the regulation of remodeling and inflammation of bone tissues through the JE gene product.
Hanazawa
S
S
Department of Oral Microbiology, Meikai University School of Dentistry, Saitama, Japan.
Takeshita
A
A
Amano
S
S
Semba
T
T
Nirazuka
T
T
Katoh
H
H
Kitano
S
S
D016475:3T3 Cells; D000818:Animals; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002999:Clone Cells; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D051379:Mice; D009000:Monocytes / Q000502:physiology*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha