PMID- 36087468 OWN - NLM STAT- MEDLINE DCOM- 20220928 LR - 20220928 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 244 DP - 2022 Oct 1 TI - FcepsilonRI deficiency alleviates silica-induced pulmonary inflammation and fibrosis. PG - 114043 LID - S0147-6513(22)00883-1 [pii] LID - 10.1016/j.ecoenv.2022.114043 [doi] AB - Silicosis is one of the most important occupational diseases worldwide, caused by inhalation of silica particles or free crystalline silicon dioxide. As a disease with high mortality, it has no effective treatment and new therapeutic targets are urgently needed. Recent studies have identified FCER1A, encoding alpha-subunit of the immunoglobulin E (IgE) receptor FcepsilonRI, as a candidate gene involved in the biological pathways leading to respiratory symptoms. FcepsilonRI is known to be important in allergic asthma, but its role in silicosis remains unclear. In this study, serum IgE concentrations and FcepsilonRI expression were assessed in pneumoconiosis patients and silica-exposed mice. The role of FcepsilonRI was explored in a silica-induced mouse model using wild-type and FcepsilonRI-deficient mice. The results showed that serum IgE concentrations were significantly elevated in both pneumoconiosis patients and mice exposed to silica compared with controls. The mRNA and protein expression of FcepsilonRI were also significantly increased in the lung tissue of patients and silica-exposed mice. FcepsilonRI deficiency significantly attenuated the changes in lung function caused by silica exposure. Silica-induced elevations of IL-1beta, IL-6, and TNF-alpha were significantly attenuated in the lung tissue and bronchoalveolar lavage fluid (BALF) of FcepsilonRI-deficient mice compared with wild-type controls. Additionally, FcepsilonRI-deficient mice showed a significantly lower score of pulmonary fibrosis than wild-type mice following exposure to silica, with significantly lower hydroxyproline content and expression of fibrotic genes Col1a1 and Fn1. Immunofluorescent staining suggested FcepsilonRI mainly on mast cells. Mast cell degranulation took place after silica exposure, as shown by increased serum histamine levels and beta-hexosaminidase activity, which were significantly reduced in FcepsilonRI-deficient mice compared with wild-type controls. Together, these data showed that FcepsilonRI deficiency had a significant protective effect against silica-induced pulmonary inflammation and fibrosis. Our findings provide new insights into the pathophysiological mechanisms of silica-induced pulmonary fibrosis and a potential target for the treatment of silicosis. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Chen, Yiling AU - Chen Y AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. FAU - Song, Meiyue AU - Song M AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. FAU - Li, Zhaoguo AU - Li Z AD - Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Hou, Lin AU - Hou L AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. FAU - Zhang, Hong AU - Zhang H AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. FAU - Zhang, Zhe AU - Zhang Z AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China; Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan 030001, China; NHC Key Laboratory of Pneumoconiosis, Taiyuan 030001, China. FAU - Hu, Huiyuan AU - Hu H AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. FAU - Jiang, Xuehan AU - Jiang X AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. FAU - Yang, Jie AU - Yang J AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. FAU - Zou, Xuan AU - Zou X AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. FAU - Pang, Junling AU - Pang J AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. FAU - Zhang, Tiantian AU - Zhang T AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. FAU - Yang, Peiran AU - Yang P AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. Electronic address: peiran.yang@foxmail.com. FAU - Wang, Jing AU - Wang J AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. Electronic address: wangjing@ibms.pumc.edu.cn. FAU - Wang, Chen AU - Wang C AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. Electronic address: wangchen@pumc.edu.cn. LA - eng PT - Journal Article DEP - 20220907 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 0 (Receptors, IgE) RN - 0 (Tumor Necrosis Factor-alpha) RN - 37341-29-0 (Immunoglobulin E) RN - 7631-86-9 (Silicon Dioxide) RN - 820484N8I3 (Histamine) RN - EC 3.2.1.52 (beta-N-Acetylhexosaminidases) RN - RMB44WO89X (Hydroxyproline) SB - IM MH - Animals MH - Fibrosis MH - Histamine/metabolism/toxicity MH - Hydroxyproline/metabolism/pharmacology/therapeutic use MH - Immunoglobulin E MH - Interleukin-6/metabolism MH - Lung MH - Mice MH - Mice, Inbred C57BL MH - *Pneumonia/pathology MH - *Pulmonary Fibrosis/chemically induced/genetics MH - RNA, Messenger/metabolism MH - Receptors, IgE/genetics/metabolism/therapeutic use MH - Silicon Dioxide/toxicity MH - *Silicosis/genetics/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - beta-N-Acetylhexosaminidases/metabolism/pharmacology/therapeutic use OTO - NOTNLM OT - FcepsilonRI OT - IgE OT - Mast cells OT - Silica OT - Silicosis COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/09/11 06:00 MHDA- 2022/09/28 06:00 CRDT- 2022/09/10 18:22 PHST- 2022/04/25 00:00 [received] PHST- 2022/08/14 00:00 [revised] PHST- 2022/08/29 00:00 [accepted] PHST- 2022/09/11 06:00 [pubmed] PHST- 2022/09/28 06:00 [medline] PHST- 2022/09/10 18:22 [entrez] AID - S0147-6513(22)00883-1 [pii] AID - 10.1016/j.ecoenv.2022.114043 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2022 Oct 1;244:114043. doi: 10.1016/j.ecoenv.2022.114043. Epub 2022 Sep 7.