title: Peroxisome Proliferator-Activated Receptor Gamma Exacerbates Concanavalin A-Induced Liver Injury via Suppressing the Translocation of NF-κB into the Nucleus.
abstract: Peroxisome proliferator-activated receptor-γ (PPARγ) has been reported to reduce inflammation and attenuate fibrosis in the liver. In this study, we investigated the effects of PPARγ on the liver injury induced by 20 mg/kg Concanavalin A (Con A). The mice were administered one of the three types of PPARγ ligands (pioglitazone, ciglitazone, and troglitazone) for 1 week, and the serum alanine aminotransferase (ALT) levels at 20 h after Con A injection were significantly elevated in the PPARγ ligand-treated mice. Furthermore, the serum ALT levels after Con A injection in the PPARγ hetero-knock-out mice (PPARγ(+/-) mice) were lower than those in the wild-type mice (WT mice). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) revealed extensive liver damage induced by Con A in the pioglitazone-treated mice. Electrophoresis mobility shift assay (EMSA) revealed that activation of translocation of nuclear factor- (NF-) κB, which is a suppressor of apoptosis, in the nucleus of the hepatocytes was suppressed in the pioglitazone-treated mice after Con A injection. In this study, we showed that PPARγ exacerbated Con A-induced liver injury via suppressing the translocation of NF-κB into the nucleus, thereby inhibiting the suppression of liver cell apoptosis.
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Wataru
authors.initials: W
authors.lastname: Tomeno
authors.forename: Kento
authors.initials: K
authors.lastname: Imajo
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Wataru
authors.initials: W
authors.lastname: Shibata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kirikoshi
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.forename: Koichiro
authors.initials: K
authors.lastname: Wada
authors.forename: Shin
authors.initials: S
authors.lastname: Maeda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima