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

Tomomi Ichikawa*, Ryuji Hayashi, Kensuke Suzuki, Shingo Imanishi, Kenta Kambara, Seisuke Okazawa, Minehiko Inomata, Toru Yamada, Yu Yamazaki, Yukiko Koshimizu, Toshiro Miwa, Shoko Matsui, Isao Usui, Masaharu Urakaze, Yuji Matsuya, Masakiyo Sasahara, Kazuyuki Tobe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

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. We investigated the effect of Sirt1 activator SRT1720 on an inflammatory model of asthma. SRT1720 suppressed inflammatory cell infiltration and cytokine production in an OVA-challenged mouse model. SRT1720 and resveratrol also directly suppressed OVA-induced splenocyte proliferation and TNF-α and IL-6 production. SRT1720 has potential as a therapeutic drug for asthma.

Original languageEnglish
Pages (from-to)332-339
Number of pages8
JournalRespirology
Volume18
Issue number2
DOIs
StatePublished - 2013/02

Keywords

  • Sirt1
  • cytokine
  • eosinophil
  • inflammation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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