PMID- 34099590 OWN - NLM STAT- MEDLINE DCOM- 20210721 LR - 20210721 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 13 IP - 11 DP - 2021 Jun 7 TI - Myeloid-specific SIRT1 deletion exacerbates airway inflammatory response in a mouse model of allergic asthma. PG - 15479-15490 LID - 10.18632/aging.203104 [doi] AB - 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 (Sirt1(fl/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 Sirt1(fl/fl)-LysMcre mice substantially enhanced airway inflammation and mucus production in response to allergen exposure. Expression of chemokine ligand (CXCL) 2, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha 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. FAU - Lai, Tianwen AU - Lai T AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. FAU - Su, Guomei AU - Su G AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. FAU - Wu, Dong AU - Wu D AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. FAU - Chen, Ziyu AU - Chen Z AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. FAU - Chen, Yujuan AU - Chen Y AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. FAU - Yi, Huajuan AU - Yi H AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. FAU - Gao, Yun AU - Gao Y AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. FAU - Chen, Cuifen AU - Chen C AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. FAU - Zeng, Man AU - Zeng M AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. FAU - Chen, Min AU - Chen M AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. FAU - Li, Dongming AU - Li D AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. FAU - Wu, Bin AU - Wu B AD - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210607 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (Allergens) RN - 0 (Cytokines) RN - EC 2.7.7.- (Cre recombinase) RN - EC 2.7.7.- (Integrases) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Allergens/adverse effects MH - Animals MH - Asthma/complications/*pathology MH - Cytokines/metabolism MH - Disease Models, Animal MH - *Gene Deletion MH - Hypersensitivity/complications/*pathology MH - Inflammation/complications/*pathology MH - Integrases/metabolism MH - Lung/*pathology MH - MAP Kinase Signaling System MH - Macrophages/metabolism/pathology MH - Mice, Transgenic MH - Myeloid Cells/*metabolism MH - Pyroglyphidae MH - Sirtuin 1/*metabolism PMC - PMC8221322 OTO - NOTNLM OT - BMDM OT - SIRT1 OT - asthma OT - macrophage COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of interest. EDAT- 2021/06/09 06:00 MHDA- 2021/07/22 06:00 PMCR- 2021/06/15 CRDT- 2021/06/08 05:58 PHST- 2020/12/27 00:00 [received] PHST- 2021/05/13 00:00 [accepted] PHST- 2021/06/09 06:00 [pubmed] PHST- 2021/07/22 06:00 [medline] PHST- 2021/06/08 05:58 [entrez] PHST- 2021/06/15 00:00 [pmc-release] AID - 203104 [pii] AID - 10.18632/aging.203104 [doi] PST - ppublish SO - Aging (Albany NY). 2021 Jun 7;13(11):15479-15490. doi: 10.18632/aging.203104. Epub 2021 Jun 7.