Inhibitory effect of pioglitazone on expression of adhesion molecules on neutrophils and endothelial cells

The interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in various inflammatory and immune diseases. It has been suggested that peroxisome proliferator‐activated receptor‐γ (PPAR‐γ, a member of the nuclear receptor superfamily of transcription factors) might be involved in the control of inflammation and in modulating the expression of various cytokines. The aim of this investigation was to evaluate the anti‐inflammatory properties of PPAR‐γ activators, as well as the inhibitory effect of PPAR‐γ on the expression of adhesion molecules on leukocytes and vascular endothelial cells. Pioglitazone, a synthetic PPAR‐γ activator, suppressed the increase of CD11b/CD18 expression on FMLP‐activated leukocytes, as detected by immunofluorescence flow cytometry. However, the FMLP‐induced elevation of cytosolic Ca+2 in leukocytes was not suppressed by pioglitazone. Pioglitazone inhibited the expression of VCAM‐1 protein and mRNA on activated human umbilical vein endothelial cells (HUVEC) after IL‐1β stimulation, as detected by ELISA and real‐time PCR. However, it showed little effect on the expression of ICAM‐1 and E‐selectin. The present study revealed that pioglitazone can influence monocyte‐EC binding by inhibiting VCAM‐1 expression on activated EC and neutrophil‐EC binding by inhibiting upregulation of CD11b/CD18 on activated neutrophils. Accordingly, pioglitazone may be useful for treating inflammatory diseases.

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