FceRI deficiency alleviates silica-induced pulmonary inflammation and fibrosis

作者：Chen, Yiling; Song, Meiyue; Li, Zhaoguo; Hou, Lin; Zhang, Hong; Zhang, Zhe; Hu, Huiyuan; Jiang, Xuehan; Yang, Jie; Zou, Xuan; Pang, Junling; Zhang, Tiantian; Yang, Peiran^*; Wang, Jing^*; Wang, Chen^*

来源：Ecotoxicology and Environmental Safety, 2022, 244: 114043.

DOI：10.1016/j.ecoenv.2022.114043

• Silicosis
• FceRI
• IgE
• Silica
• Mast cells

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 a-subunit of the immunoglobulin E (IgE) receptor FceRI, as a candidate gene involved in the biological pathways leading to respiratory symptoms. FceRI is known to be important in allergic asthma, but its role in silicosis remains unclear. In this study, serum IgE concentrations and FceRI expression were assessed in pneumoconiosis patients and silicaexposed mice. The role of FceRI was explored in a silica-induced mouse model using wild-type and FceRI-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 FceRI were also significantly increased in the lung tissue of patients and silica-exposed mice. FceRI deficiency significantly attenuated the changes in lung function caused by silica exposure. Silica-induced elevations of IL-1ll, IL-6, and TNF-a were significantly attenuated in the lung tissue and bronchoalveolar lavage fluid (BALF) of FceRI-deficient mice compared with wild-type controls. Additionally, FceRI-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 FceRI mainly on mast cells. Mast cell degranulation took place after silica exposure, as shown by increased serum histamine levels and ll-hexosaminidase activity, which were significantly reduced in FceRI-deficient mice compared with wildtype controls. Together, these data showed that FceRI 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.

• 单位
  中国医学科学院北京协和医院; 1; 哈尔滨医科大学; 西安交通大学