in mice: MCC-555 (NETOGLITAZONE) was suspended in 1.5% carboxymethylcellulose (CMC) with 0.2% Tween 20. The control group was orally gavaged with CMC alone, and the second and third groups received 30 and 60 mg/kg MCC-555 suspended in CMC for 4 weeks, respectively. Starting at 7 weeks of age, mice in all the 3 groups were injected i.p. once a week for a total of 4 weeks

It was examined the effects of a novel TZD MCC-555 on vascular cell adhesion molecule-1 (VCAM-1) expression in vascular endothelial cells (ECs). Human aortic ECs were treated with MCC-555, followed by stimulation with tumor necrosis factor (TNF)-alpha. Cell surface VCAM-1 protein expression and human monocytoid U937 cell adhesion to these cells were determined. MCC-555 efficiently inhibited TNF-alpha-stimulated VCAM-11expression and U937 cell adhesion. Transient transfection of bovine aortic ECs with a VCAM-1 promoter construct revealed that MCC-555 inhibited TNF-alpha-induced VCAM-1 promoter activity. Electrophoretic mobility-shift assay demonstrated that MCC-555 reduced the amount of nuclear factor-kappaB (NF-kappaB) bound to its recognition site on the VCAM-1 promoter. These results indicated that MCC-555 was a strong TZD agent to inhibit the cytokine-induced VCAM-1 expression in vascular ECs. The effect was exerted probably through activation of PPARalpha and/or PPARdelta, rather than PPARgamma, mediating down-regulation of NF-kappaB activity.