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Inhibitory effect of troglitazone on tumor necrosis factor alpha-induced expression of monocyte chemoattractant
M Y Ohta1, Y Nagai, T Takamura
1First Department of Internal Medicine, School of Medicine, Kanazawa University, Ishikawa, Japan.
Abstract:
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 diabetes. 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 troglitazone (1 or 10 micromol/L) in the presence or absence of tumor necrosis factor alpha (TNF-alpha) at various concentrations (50 or 500 ng/mL), and then MCP-1 secretion from the HMCs was measured. We found that TNF-alpha increased the secretion of MCP-1 by 55-fold versus the control and troglitazone significantly inhibited this TNF-alpha-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 alpha-tocopherol also inhibited TNF-alpha-induced MCP-1 production in HMCs, although its effects were not as strong as troglitazone. The present study indicates that troglitazone may prevent the progression of atherosclerosis by inhibiting MCP-1 expression in mesangial cells.
Insights
Troglitazone significantly reduces tumor necrosis factor alpha-induced monocyte chemoattractant protein-1 (MCP-1) secretion and mRNA levels in human mesangial cells, suggesting a protective role against atherosclerosis progression.
Area of Science:
- Vascular Biology
- Nephrology
- Endocrinology
Background:
- Insulin resistance is a key risk factor for atherosclerosis and glomerulosclerosis.
- Troglitazone, an oral insulin-sensitizing agent, shows potential for diabetes treatment and may mitigate vascular complications.
- The direct effects of troglitazone on vascular cells and its role in inhibiting atherosclerosis, including glomerulosclerosis, require further clarification.
Purpose of the Study:
- To investigate the effect of troglitazone on monocyte chemoattractant protein-1 (MCP-1) expression in human mesangial cells (HMCs).
- To determine if troglitazone can inhibit MCP-1 production induced by tumor necrosis factor alpha (TNF-alpha).
Main Methods:
- Human mesangial cells (HMCs) were treated with troglitazone (1 or 10 micromol/L) and/or tumor necrosis factor alpha (TNF-alpha) (50 or 500 ng/mL).
- MCP-1 secretion was measured, and MCP-1 mRNA levels were analyzed using Northern blot.
- The effect of alpha-tocopherol was also assessed as a comparative control.
Main Results:
- TNF-alpha significantly increased MCP-1 secretion by 55-fold compared to controls.
- Troglitazone markedly inhibited the TNF-alpha-induced MCP-1 secretion by 49.3%.
- Northern blot analysis confirmed that troglitazone decreased MCP-1 mRNA levels in HMCs. Alpha-tocopherol also showed inhibitory effects, though less potent than troglitazone.
Conclusions:
- Troglitazone effectively inhibits TNF-alpha-induced MCP-1 expression and secretion in human mesangial cells.
- These findings suggest that troglitazone may prevent atherosclerosis progression by modulating MCP-1 expression in mesangial cells.
