Inhibitory effect of troglitazone on tumor necrosis factor alpha—induced expression of monocyte chemoattractant protein-1 in human mesangial cells

• Published in: Metabolism, clinical and experimental Vol. 49; no. 2; pp. 163 - 166
• Main Authors: Ohta, Masayoshi Y., Nagai, Yukihiro, Takamura, Toshinari, Nohara, Erika, Kobayashi, Ken-ichi
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2000; Elsevier
• Subjects: Associated diseases and complications; Biological and medical sciences; Blotting, Northern; Cell Count - drug effects; Cell Survival - drug effects; Cells, Cultured; Chemokine CCL2 - biosynthesis; Chromans - pharmacology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme-Linked Immunosorbent Assay; Glomerular Mesangium - cytology; Glomerular Mesangium - drug effects; Glomerular Mesangium - metabolism; Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism; Humans; Hypoglycemic Agents - pharmacology; Medical sciences; RNA, Messenger - biosynthesis; Thiazoles - pharmacology; Thiazolidinediones; Troglitazone; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - pharmacology; Vitamin E - pharmacology; Endocrinopathy; Human origin; Monocyte; Mesangial cell; Diabetes mellitus; Cytokine; Cardiovascular disease; Chemotaxis; Vascular disease; Renal glomerulus; Atherosclerosis; Complication; Tumor necrosis factor α
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/S0026-0495(00)91143-0

Insulin resistance is one of the risk factors for the progression of atherosclerosis and glomerulosclerosis. Recently, the new oral insulin-sensitizing agent troglitazone has been thought to offer potential in the treatment of disease. If adopted for this use, it might be helpful in protecting against the development of atherosclerosis and microvascular complications via its improvement of insulin resistance. However, it has not yet been clarified whether troglitazone acts directly on the vascular cells and inhibits the progression of atherosclerosis, including glomerulosclerosis. Meanwhile, monocyte chemoattractant protein-1 (MCP-1) is known to play an important role in the pathogenesis of atherosclerosis and glomerulosclerosis through the induction of monocyte migration. Therefore, we investigated the effect of troglitazone on the expression of MCP-1 in human mesangial cells (HMCs). HMCs were treated with or without troglittazone (1 or 10 μmol/L) in the presence or absence of tumor necrosis factor alpha (TNF-α) at various concentrations (50 or 500 ng/mL), and then MCP-1 secretion from the HMCs was measured. We found that NTF-α increased the secretion of MCP-1 by 55-fold versus the control and troglitazone significantly inhibited this TNF-α—induced increase in MCP-1 secretion (49.3%). Moreover, Northern blot analysis showed that troglitazone decreased the MCP-1 mRNA level in HMCs. We demonstrated that α-tocopherol also inhibited TNF-α—induced MCP-1 prevent the progression of atherosclerosis by inhibiting MCP-1 expression in mesangial cells.