Expression of Histone Deacetylases 1 and It′s Effects on Histone Modifications in T Cells Isolated from Lungs of Asthmatic Wistar Rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LI Chengye , GUO Xuejun , GAN Lixing , DING Tao , GU Wen

Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University.Shanghai, 200092, ChinaCorresponding Author: GUO Xue-jun, E-mail: guoxjz@ yahoo. com. cn;

Corresponding author：

Keywords：

Asthma; T cells; Histone deacetylases 1; Histone acetylation; Histone methylation

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Objective To investigate the expression of the histone deacetylases 1( HDAC1) and the level of whole histone acetylation and methylation in lung T cells of asthmatic rats, and investigate their role in the pathogenesis of asthma.Methods Sixteen wistar rats were randomly divided into a control group and an asthma group( n =8 in each group) . The rats was sensitized with ovalbumin( OVA) and challenged with aerosol OVA to establish asthma model. The asthmatic ratmodel was confirmed by measurement of pulmonary function, histochemical staining, HE staining, and the levels of interleukin-4 ( IL-4 ) , interferon-gamma ( IFN-γ) and immunoglobulin E( IgE) in serum and bronchoalveolar lavage fluid ( BALF) . T cells were isolated fromrat lungs and the purity was identified. The expression of the HDAC1, the level of whole histone H3 and H4 acetylation, and whole H3K9 dimethylation were analyzed by Western blot in lung T cells. Results Compared with the control group, the protein expression of HDAC1 was significantly lower( 0. 465±0. 087 vs 0. 790 ±0. 076, P lt;0. 05) in lung T cells of the asthma group. No significant differences were
found in regard to the level of whole histone H3 and H4 acetylation and whole H3K9 dimethylation betweenthe two groups. Conclusions HDAC1 in lung T cells may be involved in the pathogenesis of asthma.Histone modification by HDAC1 may be a specific eventwith gene transcription which may not be associated with asthma.

Citation： LI Chengye,GUO Xuejun,GAN Lixing,DING Tao,GU Wen. Expression of Histone Deacetylases 1 and It′s Effects on Histone Modifications in T Cells Isolated from Lungs of Asthmatic Wistar Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(3): 259-263. doi: Copy

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8.	Bhavsar P, Ahmad T, Adcock IM. The role of histone deacetylases in asthma and allergic diseases. J Allergy Clin Immunol, 2008, 121 :580-584.
9.	Workman JL, Kingston RE. Alteration of nucleosome structure as a mechanismof transcriptional regulation. Annu Rev Biochem, 1998 ,67: 545-579 .
10.	Peterson S, Jackson V. Acetylation of H4 suppresses the repressive effects of the N-termini of histones H3 /H4 and facilitates the formation of positively coiled DNA. Biochemistry, 2008 , 47: 7053 -7065.
11.	Ito K, Charron CE, Adcock IM. Impact of protein acetylation in inflammatory lung diseases. Pharmacol Ther, 2007, 116 : 249-265.
12.	Bannister AJ, Kouzarides T. Reversing histone methylation. Nature,2005, 436: 1103-1106.
13.	Weichert W. HDAC expression and clinical prognosis in human malignancies. Cancer Lett, 2009, 280 : 168-176.
14.	Heinzel T, Lavinsky RM, Mullen TM, et al. A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature, 1997 , 387: 43-48 .
15.	Moreira JM, Scheipers P, S??rensen P. The histone deacetylase inhibitor Trichostatin A modulates CD4 + T cell responses. BMC Cancer, 2003 , 3: 30 .
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17.	Ma P, Schultz RM. Histone deacetylase 1 ( HDAC1 ) regulates histone acetylation, development, and gene expression in preimplantation mouse embryos. Dev Biol, 2008, 319 : 110-120.

1. Kaminuma O, Kitamura F, Miyatake S, et al. T-box 21 transcription factor is responsible for distorted T( H) 2 differentiation in human peripheral CD4 + T cells. J Allergy Clin Immunol,2009, 123: 813-23.
2. Su RC, Becker AB, Kozyrskyj AL, et al. Epigenetic regulation of established human type 1 versus type 2 cytokine responses. JAllergyClin Immunol, 2008, 121: 57-63.
3. 李成业, 甘丽杏, 郭雪君. 支气管哮喘的表观遗传学. 中华结核和呼吸杂志, 2009, 32 : 759-761.
4. Ito K, Caramori G, Lim S, et al. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med, 2002, 166 : 392-396.
5. Miller RL, Ho SM. Environmental Epigenetics and Asthma. Am J Respir Crit Care Med, 2008 , 177: 567-573 .
6. El-Biaze M, Boniface S, Koscher V, et al. T cell activation, from atopy to asthma: more a paradox. Allergy, 2003 , 58: 844-853.
7. Marmorstein R. Protein modules that manipulate histone tails for chromatin regulation. Nat Rev Mol Cell Biol, 2001, 2: 422-432.
8. Bhavsar P, Ahmad T, Adcock IM. The role of histone deacetylases in asthma and allergic diseases. J Allergy Clin Immunol, 2008, 121 :580-584.
9. Workman JL, Kingston RE. Alteration of nucleosome structure as a mechanismof transcriptional regulation. Annu Rev Biochem, 1998 ,67: 545-579 .
10. Peterson S, Jackson V. Acetylation of H4 suppresses the repressive effects of the N-termini of histones H3 /H4 and facilitates the formation of positively coiled DNA. Biochemistry, 2008 , 47: 7053 -7065.
11. Ito K, Charron CE, Adcock IM. Impact of protein acetylation in inflammatory lung diseases. Pharmacol Ther, 2007, 116 : 249-265.
12. Bannister AJ, Kouzarides T. Reversing histone methylation. Nature,2005, 436: 1103-1106.
13. Weichert W. HDAC expression and clinical prognosis in human malignancies. Cancer Lett, 2009, 280 : 168-176.
14. Heinzel T, Lavinsky RM, Mullen TM, et al. A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature, 1997 , 387: 43-48 .
15. Moreira JM, Scheipers P, S??rensen P. The histone deacetylase inhibitor Trichostatin A modulates CD4 + T cell responses. BMC Cancer, 2003 , 3: 30 .
16. Choi JH, Oh SW, Kang MS, et al. Trichostatin A attenuates airway inflammation in mouse asthma model. Clin Exp Allergy, 2005, 35 :89-96.
17. Ma P, Schultz RM. Histone deacetylase 1 ( HDAC1 ) regulates histone acetylation, development, and gene expression in preimplantation mouse embryos. Dev Biol, 2008, 319 : 110-120.

Chinese Journal of Respiratory and Critical Care Medicine

Expression of Histone Deacetylases 1 and It′s Effects on Histone Modifications in T Cells Isolated from Lungs of Asthmatic Wistar Rats

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