Affiliations: Inflammation and Immunology, Kyoto Prefectural
University of Medicine, Kyoto, Japan | Molecular Gastroenterology and Hepatology, Graduate
School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto,
602-8566, Japan
Note: [] Address for correspondence: Norimasa Yoshida, MD, PhD, Molecular
Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine,
Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Tel.: +81 75 251 5508;
Fax: +81 75 252 3721; E-mail: [email protected]
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-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.
