Original Article
Role of STAT3-RORγt-IL-17 signaling pathway in neutrophil asthma mice
Cui Caiyun, Wei Guilian, Liu Chunyun, Guo Shangde, He Ronghua, Ma Xiaojun, Kang Yaowen, Yi Yali
Published 2022-11-20
Cite as Int J Respir, 2022, 42(22): 1700-1706. DOI: 10.3760/cma.j.cn131368-20220316-00198
Abstract
ObjectiveTo investigate the mechanism of signal transducer and activator of transcription 3 (STAT3)-retinoic acid-related orphan receptor gamma t (RORγt)-interleukin-17(IL-17) signaling pathway in airway inflammation in neutrophil asthma mice.
MethodsThis was an experimental study.A total of 36 female BALB/C mice were randomly divided into three groups: neutrophilic asthma group, eosinophilic asthma group, and normal control group.The eosinophilic asthma model was sensitized by intraperitoneal injecting ovalbumin (OVA) and challenged with an aerosol of OVA.The neutrophilic asthma model was sensitized by OVA and intranasal infusion of lipopolysaccharide, challenged with an aerosol of OVA.The normal control group was sensitized and challenged by normal saline instead of OVA.Bronchoalveolar lavage fluid (BALF) was collected and the total number of the cells was counted.After HE staining, the cells were classified and the numbers counted.Pathological changes of lung tissue were observed after HE staining, STAT3 and RORγt were detected by immunohistochemistry, and the proportion of Th17 cells in lung tissue was detected by flow cytometry.The levels of IL-17 and IL-6 in serum and BALF were detected by enzyme linked immunosorbent assay.
ResultsCompared with normal control group, the eosinophilic asthma group had significant airway inflammatory cell infiltration, increased total number of BALF cells and proportion of neutrophils (P<0.01), raised levels of IL-17 and IL-6 in BALF and serum (P<0.05), and elevated proportion of CD4+ IL-17+ T cells (P<0.01). Compared with the eosinophilic asthma group, the neutrophilic asthma group showed increased airway inflammatory cells, elevated total number of BALF cells and proportion of neutrophils (P<0.05), decreased proportion of eosinophils (P<0.05), increased levels of IL-17 and IL-6 in serum and BALF, and enhanced proportion of CD4+ IL-17+ T cells (P<0.05). Compared with the normal control and eosinophilic asthma groups, the neutrophilic asthma group manifested elevated expressions of STAT3 and RORγt in lung tissue (P<0.05).
ConclusionsSTAT3-RORγt-IL-17 signaling pathway is involved in the pathogenesis of different inflammatory phenotypes of asthma and plays a more important role in the pathogenesis of neutrophilic asthma.
Key words:
Asthma; Neutrophil; Signal transducer and activator of transcription 3; Retinoic acid-related orphan receptor gamma t; Interleukin-17
Contributor Information
Cui Caiyun
Department of Respiratory and Critical Care Medicine, the Fifth People′s Hospital of Datong, Datong 037006, China
Wei Guilian
Department of Respiratory and Critical Care Medicine, the Fifth People′s Hospital of Datong, Datong 037006, China
Liu Chunyun
Institute of Respiratory and Occupational Diseases, Shanxi Datong University, Datong 037009, China
Guo Shangde
Institute of Respiratory and Occupational Diseases, Shanxi Datong University, Datong 037009, China
He Ronghua
Department of Pathology, Coal General Hospital, Datong 037006, China
Ma Xiaojun
Department of Respiratory and Critical Care Medicine, the Fifth People′s Hospital of Datong, Datong 037006, China
Kang Yaowen
Department of Respiratory and Critical Care Medicine, the Fifth People′s Hospital of Datong, Datong 037006, China
Yi Yali
Department of Respiratory and Critical Care Medicine, the Fifth People′s Hospital of Datong, Datong 037006, China
