Biomaterial Database

TGF-beta induces expression of monocyte chemoattractant JE/monocyte chemoattractant protein 1 via transcriptional factor AP-1 induced by protein kinase in osteoblastic cells. 1995

A Takeshita, and Y Chen, and A Watanabe, and S Kitano, and S Hanazawa

Department of Oral Microbiology, Meikai University School of Dentistry, Saitama, Japan.

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.

UI	MeSH Term	Description	Entries
D007546	Isoquinolines	A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010006	Osteoblasts	Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.	Osteoblast
D010879	Piperazines	Compounds that are derived from PIPERAZINE.
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011494	Protein Kinases	A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.	Protein Kinase,Kinase, Protein,Kinases, Protein
D002630	Chemotactic Factors	Chemical substances that attract or repel cells. The concept denotes especially those factors released as a result of tissue injury, microbial invasion, or immunologic activity, that attract LEUKOCYTES; MACROPHAGES; or other cells to the site of infection or insult.	Chemoattractant,Chemotactic Factor,Chemotaxin,Chemotaxins,Cytotaxinogens,Cytotaxins,Macrophage Chemotactic Factor,Chemoattractants,Chemotactic Factors, Macrophage,Macrophage Chemotactic Factors,Chemotactic Factor, Macrophage,Factor, Chemotactic,Factor, Macrophage Chemotactic
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man