Stimulation of the peroxisome proliferator-activated receptor γ (PPARγ) and the expression of selected blood monocyte cytokine genes in diabetic macroangiopathy

Monocytes and macrophages play a key role in the progression of atheromatous changes. The peroxisome proliferator-activated receptor γ (PPARγ) can limit macroangiopathy through the control of cytokine transcription. The objectives of this study were to examine the influence of PPARγ and its agonist (rosiglitazone) on the TNFα, IL-6, IL-8 and IL-10 gene expression in monocytes of patients with diabetic macroangiopathy and to analyse obtained results in context of selected atherogenic factors ant direct indicators of endothelial lesion. TNFα, IL-6, IL-8, IL-10 and PPARγ gene expression was assessed in peripheral blood monocytes in 45 patients with type 2 diabetes before and following 22 weeks of rosiglitazone therapy (real-time PCR [Applied Biosystems]). As indicators of endothelial lesion, concentration of thrombomodulin (immunoassay [Diagnostica Stago®]) and amount of circulating blood endothelial cells (immunofluorescence method with MoAb CLB-HEC19) were determined. Following rosiglitazone therapy, a statistically significant downward tendency of TNFα (p = 0.026) and IL-8 (p = 0.008) gene expression was noted. Before and following rosiglitazone treatment, PPARγ, IL-6 and IL-10 gene expression was undetectable in studied monocytes in vivo. In conclusion, TNFα and IL-8 play an important role in monocyte atherogenic activity. Rosiglitazone reduces monocyte proinflammatory readiness by influencing the expression of selected atherogenic cytokines (PPARγ-independent pathway).