HDAC2 attenuates airway inflammation by suppressing IL-17A production in HDM-challenged mice
Autor: | Wen Li, Songmin Ying, Chao Zhang, Xufei Du, Luanqing Che, Chao Cao, Bin Wu, Yanping Wu, Nanxia Xuan, Yong Wang, Feng Xu, Zhihua Chen, Mindan Wu, Tianwen Lai, Huahao Shen |
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Rok vydání: | 2019 |
Předmět: |
Male
Pulmonary and Respiratory Medicine Allergic airway inflammation Physiology Histone Deacetylase 2 Mice Th2 Cells Physiology (medical) Animals Medicine Asthma Mice Knockout business.industry Histone deacetylase 2 Interleukin-17 Pyroglyphidae Airway inflammation Cell Biology medicine.disease Disease Models Animal Immunology Respiratory epithelium Female Histone deacetylase business |
Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 316:L269-L279 |
ISSN: | 1522-1504 1040-0605 |
Popis: | Histone deacetylase (HDAC)2 is expressed in airway epithelium and plays a pivotal role in inflammatory cells. However, the role of HDAC2 in allergic airway inflammation remains poorly understood. In the present study, we determined the role of HDAC2 in airway inflammation using in vivo models of house dust mite (HDM)-induced allergic inflammation and in vitro cultures of human bronchial epithelial (HBE) cells exposed to HDM, IL-17A, or both. We observed that HDM-challenged Hdac2+/− mice exhibited substantially enhanced infiltration of inflammatory cells. Higher levels of T helper 2 cytokines and IL-17A expression were found in lung tissues of HDM-challenged Hdac2+/− mice. Interestingly, IL-17A deletion or anti-IL-17A treatment reversed the enhanced airway inflammation induced by HDAC2 impairment. In vitro, HDM and IL-17A synergistically decreased HDAC2 expression in HBE cells. HDAC2 gene silencing further enhanced HDM- and/or IL-17A-induced inflammatory cytokines in HBE cells. HDAC2 overexpresion or blocking IL-17A gene expression restored the enhanced inflammatory cytokines. Collectively, these results support a protective role of HDAC2 in HDM-induced airway inflammation by suppressing IL-17A production and might suggest that activation of HDAC2 and/or inhibition of IL-17A production could prevent the development of allergic airway inflammation. |
Databáze: | OpenAIRE |
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