Sirtuin 1 activator SRT1720 suppresses inflammation in an ovalbumin-induced mouse model of asthma.
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.
First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. tomichz@gmail.com
Tomomi
T
Ichikawa
Ryuji
R
Hayashi
Kensuke
K
Suzuki
Shingo
S
Imanishi
Kenta
K
Kambara
Seisuke
S
Okazawa
Minehiko
M
Inomata
Toru
T
Yamada
Yu
Y
Yamazaki
Yukiko
Y
Koshimizu
Toshiro
T
Miwa
Shoko
S
Matsui
Isao
I
Usui
Masaharu
M
Urakaze
Yuji
Y
Matsuya
Masakiyo
M
Sasahara
Kazuyuki
K
Tobe
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D006576:Heterocyclic Compounds, 4 or More Rings; D012333:RNA, Messenger; C525422:SRT1720; D013267:Stilbenes; D010047:Ovalbumin; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol