title: Inhibitory effect of pioglitazone on expression of adhesion molecules on neutrophils and endothelial cells.
abstract: 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-gamma (PPAR-gamma, 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-gamma activators, as well as the inhibitory effect of PPAR-gamma on the expression of adhesion molecules on leukocytes and vascular endothelial cells. Pioglitazone, a synthetic PPAR-gamma 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 Ca2+ 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-1beta 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.
authors.affiliation: Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Imamoto
authors.forename: Norimasa
authors.initials: N
authors.lastname: Yoshida
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kuroda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Toru
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D015703:Antigens, CD / Q000097:blood; D001483:Base Sequence; D002118:Calcium / Q000097:blood; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D017931:DNA Primers; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D000077205:Pioglitazone; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D019040:E-Selectin; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002118:Calcium; D000077205:Pioglitazone