PMID- 35149050 OWN - NLM STAT- MEDLINE DCOM- 20220425 LR - 20220425 IS - 1873-2968 (Electronic) IS - 0006-2952 (Linking) VI - 198 DP - 2022 Apr TI - Interfering with alternatively activated macrophages by CSF-1R inhibition exerts therapeutic capacity on allergic airway inflammation. PG - 114952 LID - S0006-2952(22)00046-6 [pii] LID - 10.1016/j.bcp.2022.114952 [doi] AB - PURPOSE: Allergic asthma is a chronic inflammatory disorder with airway hyperresponsiveness and tissue remodeling as the main pathological characteristics. The etiology of asthma is relatively complicated, involving genetic susceptibility, epigenetic regulation, environmental factors, and immune imbalance. Colony stimulating factor 1 receptor (CSF-1R), highly expressed in myeloid monocytes, plays an important role in regulating inflammation. However, the pathological role of CSF-1R and the therapeutic effects of CSF-1R inhibitor in allergic airway inflammation remain indistinct. METHODS: The house dust mite (HDM)-triggered allergic airway inflammation model was conducted to fully uncover the efficacies of CSF-1R inhibition, as illustrated by histopathological examinations, biochemical analysis, ELISA, RT-PCR, Western blotting assay, immunofluorescence, and flow cytometry. Furthermore, bone marrow-derived macrophages (BMDMs) were differentiated and polarized upon IL-4/IL-13 induction to clarify the underlying mechanisms of CSF-1R inhibition. RESULTS: Herein, we presented that the expression of CSF-1R was increased in HDM-induced experimental asthma and inhibition of CSF-1R displayed dramatic effects on the disease severity of asthma, referring to suppressing the secretion of allergic mediators, dysfunction of airway epithelium, and infiltration of inflammatory cells. Furthermore, CSF-1R inhibitor could markedly restrain the polarization and expression of transcriptional factors of alternatively activated macrophages (AAMs) in the presence of IL-4/IL-13 and reduce the recruitment of CSF-1R-dominant macrophages, both in acute and chronic allergic airway inflammation model. CONCLUSION: Collectively, our findings demonstrated the molecular pathological mechanism of CSF-1R in allergic airway diseases and suggested that targeting CSF-1R might be an alternative intervention strategy on the homeostasis of airway immune microenvironment in asthma. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Xiang, Caigui AU - Xiang C AD - Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Fan, Chen AU - Fan C AD - Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. FAU - Lu, Qiukai AU - Lu Q AD - Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Liu, Moting AU - Liu M AD - Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Lu, Huimin AU - Lu H AD - Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Feng, Chunlan AU - Feng C AD - Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. FAU - Wu, Yanwei AU - Wu Y AD - Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. FAU - Wu, Bing AU - Wu B AD - Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Li, Heng AU - Li H AD - Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: cpuliheng@126.com. FAU - Tang, Wei AU - Tang W AD - Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: tangwei@simm.ac.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220209 PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (Interleukin-13) RN - 207137-56-2 (Interleukin-4) SB - IM MH - Animals MH - *Asthma/metabolism MH - Disease Models, Animal MH - Epigenesis, Genetic MH - *Hypersensitivity/metabolism MH - Inflammation MH - Interleukin-13/metabolism MH - Interleukin-4/metabolism MH - Lung/metabolism MH - Macrophages/metabolism MH - Pyroglyphidae OTO - NOTNLM OT - Allergy OT - Asthma OT - CSF-1R OT - Inflammation OT - Macrophages EDAT- 2022/02/13 06:00 MHDA- 2022/04/26 06:00 CRDT- 2022/02/12 05:28 PHST- 2021/12/24 00:00 [received] PHST- 2022/02/04 00:00 [revised] PHST- 2022/02/04 00:00 [accepted] PHST- 2022/02/13 06:00 [pubmed] PHST- 2022/04/26 06:00 [medline] PHST- 2022/02/12 05:28 [entrez] AID - S0006-2952(22)00046-6 [pii] AID - 10.1016/j.bcp.2022.114952 [doi] PST - ppublish SO - Biochem Pharmacol. 2022 Apr;198:114952. doi: 10.1016/j.bcp.2022.114952. Epub 2022 Feb 9.