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- Title
Sirtuin 1 activator SRT1720 suppresses inflammation in an ovalbumin-induced mouse model of asthma.
- 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
- Abstract
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 < 0.01). In OVA mice, SRT1720 treatment decreased total and eosinophil cell counts and IL-5 and IL-13 levels in the BAL fluid compared with the vehicle treatment ( P < 0.05). In OVA mice, SRT1720 treatment also decreased inflammatory cell lung infiltrates histologically ( P = 0.002). Both SRT1720 and resveratrol suppressed OVA-induced cell proliferation and IL-6 ( P < 0.05) and tumour necrosis factor-α (TNF-α) ( P < 0.05) production in splenocytes ( P < 0.01). Conclusions: The Sirt1 activator SRT1720 suppressed inflammatory cell infiltration and cytokine production in an OVA-induced mouse model of asthma. SRT1720 and resveratrol suppressed OVA-induced splenocyte proliferation and TNF-α and IL-6 production. Sirt1 activators might have beneficial effects in asthmatics by suppressing inflammation.
- Subjects
SIRTUINS; OVALBUMINS; LABORATORY mice; ASTHMA treatment; TREATMENT effectiveness; HISTONE deacetylase; HISTONE acetyltransferase
- Publication
Respirology, 2013, Vol 18, Issue 2, p332
- ISSN
1323-7799
- Publication type
Article
- DOI
10.1111/j.1440-1843.2012.02284.x