Research Paper Volume 13, Issue 11 pp 15479—15490
Myeloid-specific SIRT1 deletion exacerbates airway inflammatory response in a mouse model of allergic asthma
- 1 Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
Received: December 27, 2020 Accepted: May 13, 2021 Published: June 7, 2021https://doi.org/10.18632/aging.203104
How to Cite
Copyright: © 2021 Lai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sirtuin 1 (SIRT1) is a class III histone deacetylase that exerts an anti-inflammatory effect in airway diseases. Activated macrophages play an important role in asthma. However, the roles of SIRT1 on allergic airway inflammation in macrophages remain largely unexplored. In this study, we aimed to determine the roles of SIRT1 on allergic airway inflammation in macrophages. The effect of myeloid-specific SIRT1 deletion (Sirt1fl/fl-LysMcre) on airway inflammation was assessed by using in vivo models of asthma following allergen exposure and in vitro culture of primary bone marrow–derived macrophages (BMDMs) exposed to house dust mite (HDM). We observed that Sirt1fl/fl-LysMcre mice substantially enhanced airway inflammation and mucus production in response to allergen exposure. Expression of chemokine ligand (CXCL) 2, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α were reduced in BMDMs with myeloid-specific deletion of Sirt1 after stimulation of HDM. Moreover, SIRT1 suppressed the inflammatory cytokines expression in BMDMs partially via the ERK/p38 MAPK pathways. Our study demonstrated that SIRT1 suppresses the allergic airway inflammation in macrophages, and suggested that activation of SIRT1 in macrophages may represent therapeutic strategy for asthma.
BMDM: bone marrow-derived macrophage; AM: alveolar macrophage; HDM: house dust mite; CXCL2: chemokine ligand 2; MAPK: mitogen-activated protein kinase.