Open AccessHistone deacetylase inhibitor regulates the balance of Th 17/Treg in allergic asthma
Author(s) -
Hou Xiaoxia,
Wan Huanying,
Ai Xiangyan,
Shi Yuheng,
Ni Yingmeng,
Tang Wei,
Shi Guochao
Publication year - 2016
Publication title -
the clinical respiratory journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.789
H-Index - 33
eISSN - 1752-699X
pISSN - 1752-6981
DOI - 10.1111/crj.12227
Subject(s) - foxp3 , rar related orphan receptor gamma , trichostatin a , histone deacetylase inhibitor , medicine , histone deacetylase , immunology , interleukin 4 , downregulation and upregulation , microbiology and biotechnology , immunoglobulin e , cytokine , biology , antibody , histone , immune system , biochemistry , gene
Background and Aims The aim of this study is to investigate the expression pattern of histone deacetylase 9 in peripheral blood of patients with allergic asthma and its regulatory effect on the balance of Th 17/Treg cells involved in the pathogenesis of asthma. Methods flap‐Ub promoter‐GFP‐WRE vector was used to construct the J urkat‐ HA ‐ FOXP 3 cell line. After histone deacetylase inhibitor‐trichostatin A ( TSA ) treatment, FOXP 3 and ROR γt expression were detected by real‐time‐polymerase chain reaction ( RT ‐ PCR ). BALB /c mice were randomly assigned to control group, TSA treatment and the asthma group. Serum Immunoglobulin E (IgE) was detected with enzyme‐linked immunosorbent assay ( ELISA ), airway inflammation in lung tissue evaluated by haematoxylin/eosin staining, bronchoalveolar lavage fluid ( BALF ) cell number and differential counted, interleukin ( IL )‐17 A and TGF ‐β concentrations in BALF measured with ELISA , and expression of ROR γt and FOXP 3 messenger RNA ( mRNA )measured by RT ‐ PCR . Forty‐seven patients with asthma were recruited and assigned to intermittent, mild and moderate–severe group. GATA 3, IL ‐4, histone deacetylases ( HDAC ) 9 mRNA expression level were measured by RT ‐ PCR . Results After TSA treatment, FOXP 3 mRNA level was upregulated, while ROR γt mRNA level was downregulated. FOXP 3 protein level was also upregulated by TSA . In vivo , TSA treatment can inhibit IL ‐17 but promote transforming growth factor‐beta production in the BALF of asthma mice, and inhibited the expression of Th 17 cells and ROR γt mRNA in lung; also can promote Foxp 3 mRNA expression. GATA 3, IL ‐4 mRNA expression levels were upregulated in patients with asthma than the healthy control. HDAC 9 mRNA expression level was associated with the severity of disease. Conclusion The histone deacetylase inhibitor TSA can regulate the balance of Th 17/Treg in asthma by regulating the activity of histone deacetylase.