Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma
Background: Accumulating evidence indicated the crucial role for interleukin 6 (IL-6) signaling in the development of allergic asthma. Yet, the role of IL-6 signaling in toluene diisocyanate (TDI)-induced mixed granulocytic airway inflammation still remains unclear. Thus, the aims of this study were...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Allergology International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1323893021000800 |
| _version_ | 1818943661062225920 |
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| author | Shuyu Chen Zhuoyu Chen Yao Deng Shanshan Zha Li Yu Difei Li Zhenyu Liang Kai Yang Shengming Liu Rongchang Chen |
| author_facet | Shuyu Chen Zhuoyu Chen Yao Deng Shanshan Zha Li Yu Difei Li Zhenyu Liang Kai Yang Shengming Liu Rongchang Chen |
| author_sort | Shuyu Chen |
| collection | DOAJ |
| description | Background: Accumulating evidence indicated the crucial role for interleukin 6 (IL-6) signaling in the development of allergic asthma. Yet, the role of IL-6 signaling in toluene diisocyanate (TDI)-induced mixed granulocytic airway inflammation still remains unclear. Thus, the aims of this study were to dissect the role of IL-6 signaling and to evaluate the effect of tocilizumab on TDI-induced steroid-resistant asthma. Methods: TDI-induced asthma model was prepared and asthmatic mice were respectively given IL-6 monoclonal antibody, IL-6R monoclonal antibody (tocilizumab, 5 mg/kg, i.p. after each challenge) for therapeutic purposes or isotype IgG as control. Results: TDI exposure just elevated IL-6R expression in the infiltrated inflammatory cells around the airway, but increased glycoprotein 130 expression in the whole lung, especially in bronchial epithelium. Moreover, TDI inhalation increased airway hyperresponsiveness (AHR) to methacholine, coupled with mixed granulocytic inflammation, exaggerated epithelial denudation, airway smooth muscle thickening, goblet cell metaplasia, extensive submucosal collagen deposition, dysregulated Th2/Th17 responses, as well as innate immune responses and raised serum IgE. And almost all these responses except for raised serum IgE were markedly ameliorated by the administration of IL-6 neutralizing antibody or tocilizumab, but exhibited poor response to systemic steroid treatment. Also, TDI challenge induced nucleocytoplasm translocation of HMGB1 and promoted its release in the BALF, as well as elevated lung level of STAT3 phosphorylation, which were inhibited by anti-IL-6 and anti-IL-6R treatment. Conclusions: Our data suggested that IL-6 monoclonal antibody and tocilizumab might effectively abrogate TDI-induced airway inflammation and remodeling, which could be used as a clinical potential therapy for patients with severe asthma. |
| first_indexed | 2024-12-20T07:30:52Z |
| format | Article |
| id | doaj.art-25397ac636b84b3ab3d0058a886ca93c |
| institution | Directory Open Access Journal |
| issn | 1323-8930 |
| language | English |
| last_indexed | 2024-12-20T07:30:52Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Allergology International |
| spelling | doaj.art-25397ac636b84b3ab3d0058a886ca93c2022-12-21T19:48:25ZengElsevierAllergology International1323-89302022-01-017117382Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthmaShuyu Chen0Zhuoyu Chen1Yao Deng2Shanshan Zha3Li Yu4Difei Li5Zhenyu Liang6Kai Yang7Shengming Liu8Rongchang Chen9Department of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), The First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen, China; Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Clinical Laboratory, Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, ChinaDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), The First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen, ChinaDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), The First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen, ChinaDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), The First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen, ChinaDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), The First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen, ChinaThe First Affiliated Hospital, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, ChinaDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), The First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen, China; Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Jinan University, Guangzhou, China; Corresponding author.Department of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), The First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen, China; Corresponding author. Department of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), The First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen, 518020, China.Background: Accumulating evidence indicated the crucial role for interleukin 6 (IL-6) signaling in the development of allergic asthma. Yet, the role of IL-6 signaling in toluene diisocyanate (TDI)-induced mixed granulocytic airway inflammation still remains unclear. Thus, the aims of this study were to dissect the role of IL-6 signaling and to evaluate the effect of tocilizumab on TDI-induced steroid-resistant asthma. Methods: TDI-induced asthma model was prepared and asthmatic mice were respectively given IL-6 monoclonal antibody, IL-6R monoclonal antibody (tocilizumab, 5 mg/kg, i.p. after each challenge) for therapeutic purposes or isotype IgG as control. Results: TDI exposure just elevated IL-6R expression in the infiltrated inflammatory cells around the airway, but increased glycoprotein 130 expression in the whole lung, especially in bronchial epithelium. Moreover, TDI inhalation increased airway hyperresponsiveness (AHR) to methacholine, coupled with mixed granulocytic inflammation, exaggerated epithelial denudation, airway smooth muscle thickening, goblet cell metaplasia, extensive submucosal collagen deposition, dysregulated Th2/Th17 responses, as well as innate immune responses and raised serum IgE. And almost all these responses except for raised serum IgE were markedly ameliorated by the administration of IL-6 neutralizing antibody or tocilizumab, but exhibited poor response to systemic steroid treatment. Also, TDI challenge induced nucleocytoplasm translocation of HMGB1 and promoted its release in the BALF, as well as elevated lung level of STAT3 phosphorylation, which were inhibited by anti-IL-6 and anti-IL-6R treatment. Conclusions: Our data suggested that IL-6 monoclonal antibody and tocilizumab might effectively abrogate TDI-induced airway inflammation and remodeling, which could be used as a clinical potential therapy for patients with severe asthma.http://www.sciencedirect.com/science/article/pii/S1323893021000800Airway inflammationIL-6 signalingSteroid-resistant asthmaNeutralizing antibodyToluene diisocyanate |
| spellingShingle | Shuyu Chen Zhuoyu Chen Yao Deng Shanshan Zha Li Yu Difei Li Zhenyu Liang Kai Yang Shengming Liu Rongchang Chen Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma Allergology International Airway inflammation IL-6 signaling Steroid-resistant asthma Neutralizing antibody Toluene diisocyanate |
| title | Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma |
| title_full | Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma |
| title_fullStr | Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma |
| title_full_unstemmed | Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma |
| title_short | Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma |
| title_sort | prevention of il 6 signaling ameliorates toluene diisocyanate induced steroid resistant asthma |
| topic | Airway inflammation IL-6 signaling Steroid-resistant asthma Neutralizing antibody Toluene diisocyanate |
| url | http://www.sciencedirect.com/science/article/pii/S1323893021000800 |
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