Sirtuin 1 activator SRT1720 suppresses inflammation in an ovalbumin-induced mouse model of asthma

• Published in: Respirology (Carlton, Vic.) Vic.), 2013-02, Vol.18 (2), p.332-339
• Main Authors: ICHIKAWA, TOMOMI, HAYASHI, RYUJI, SUZUKI, KENSUKE, IMANISHI, SHINGO, KAMBARA, KENTA, OKAZAWA, SEISUKE, INOMATA, MINEHIKO, YAMADA, TORU, YAMAZAKI, YU, KOSHIMIZU, YUKIKO, MIWA, TOSHIRO, MATSUI, SHOKO, USUI, ISAO, URAKAZE, MASAHARU, MATSUYA, YUJI, SASAHARA, MASAKIYO, TOBE, KAZUYUKI
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Asthma - chemically induced; Asthma - metabolism; Asthma - prevention & control; cytokine; Cytokines - metabolism; Disease Models, Animal; eosinophil; Female; Heterocyclic Compounds, 4 or More Rings - administration & dosage; Heterocyclic Compounds, 4 or More Rings - pharmacology; Heterocyclic Compounds, 4 or More Rings - therapeutic use; inflammation; Lung - metabolism; Lung - pathology; Mice; Mice, Inbred BALB C; Ovalbumin - adverse effects; Pneumonia - chemically induced; Pneumonia - metabolism; Pneumonia - prevention & control; Respiratory System - drug effects; Respiratory System - metabolism; Respiratory System - physiopathology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sirt1; Sirtuin 1 - drug effects; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Stilbenes - pharmacology; Stilbenes - therapeutic use
• ISSN: 1323-7799; 1440-1843
• DOI: 10.1111/j.1440-1843.2012.02284.x

ABSTRACT Background and objective:  In asthma, reduced histone deacetylase activity and enhanced histone acetyltransferase activity in the lungs have been reported. However, the precise function of Sirtuin 1 (Sirt1), a class III histone deacetylase, and the effect of the Sirt1 activator SRT1720 on allergic inflammation have not been fully elucidated. Methods:  The effect of SRT1720, a synthetic activator of Sirt1, in an ovalbumin (OVA)‐induced asthma mouse model was investigated. The effect of SRT1720 and resveratrol on OVA stimulation in splenocytes from OVA‐sensitized and challenged mice was also examined. Results:  In OVA‐sensitized and challenged mice (OVA mice) compared with saline‐sensitized and challenged mice (control mice), Sirt1 messenger RNA expression in the lungs was decreased (P = 0.02), while cellular infiltration, airway eosinophilia and bronchoalveolar lavage (BAL) fluid levels of interleukin (IL)‐4, IL‐5 and IL‐13 were increased (P