Abstract：Objective To evaluate the roles of various cytokines, histone acetyltransferase (HAT) and histone deacetylase (HDAC) in the pathogenesis of bronchial asthma. Methods BALB/C mice were randomly assigned to control, untreated asthma, hormone treatment and TSA treatment groups. Bronchial asthma was induced by intraperitoneal injections and atomization inhalation of ovalbumin (OVA) in the asthma, hormone treatment and trichostatin (TSA) treatment groups. The mice in the hormone treatment and TSA treatment groups were administered with dexamethasone 1.0 mg/kg and TSA 1.0 mg/kg respectively by an intraperitoneal injection 30 minutes before challenge of asthma. At 24 hours after the last challenge, IL-4, IL-8 and IFN- levels in serum were measured using ELISA, and activities of HAT and HDAC in peripheral blood mononuclear cells (PBMC) were determined by the enzyme linked immunofluorescence assay. Results The serum levels of IL-4 and IL-8 in the untreated asthma group were higher than in the control, hormone treatment and TSA treatment groups (P<0.05). There was no difference in the serum levels of IL-4 and IL-8 among the control, hormone treatment and TSA treatment groups (P>0.05). The activity of HDAC in the untreated asthma group was lower than in the control, hormone treatment and TSA treatment groups (P<0.05). Hormone treatment significantly decreased the activity of HAT compared with the untreated asthma group (P<0.05). There was no difference in the activities of HAT and HDAC among the control, hormone treatment and TSA treatment groups (P>0.05). Conclusions The decreased activity of HDAC leads to an increased secretion of inflammatory factors and thus induces asthma.
LI Ling,PAN Zhen-Zhen,HE Jian et al. Roles of histone acetyltransferase and histone deacetylase in the pathogenesis of bronchial asthma[J]. CJCP, 2015, 17(6): 629-633.
Kuo CH, Hsieh CC, Lee MS, et al. Epigenetic regulation in allergic diseases and related studies[J]. Asia Pac Allergy, 2014, 4(1):14-18.
[2]
García MP, García-García A. Epigenome and DNA methylation in oral squamous cell carcinoma[J]. Methods Mol Biol, 2012, 863:207-219.
[3]
Kouzarides T. Chromatin modifications and their function[J]. Cell, 2007, 128(4):693-705.
[4]
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[J]. Biochemistry, 2008, 47(27):7053-7065.
[5]
Cui ZL, Gu W, Ding T, et al. Histone modifications of Notch1 promoter affect lung CD4+T cell differentiation in asthmatic rats[J]. Int J Immunopathol Pharmacol, 2013, 26(2):371-381.
[6]
Hew M, Bhavsar P, Torrego A, et al. Relative corticosteroid insensitivity of peripheral blood mononuclear cells in severe asthma[J]. Am J Respir Crit Care Med, 2006, 174(2):134-141.
[7]
Barnes PJ. How corticosteroids control inflammation:Quintiles Prize Lecture 2005[J]. Br J Pharmacol, 2006, 148(3):245-254.
[8]
Butler CA, McQuaid S, Taggart CC, et al. Glucocorticoid receptor β and histone deacetylase 1 and 2 expression in the airways of severe asthma[J]. Thorax, 2012, 67(5):392-398.
[9]
Barnes PJ, Ito K, Adcock IM. Corticosteroid resistance in chronic obstructive pulmonary disease:inactivation of histone deacetylase[J]. Lancet, 2004, 363(9410):731-733.
[10]
Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory diseases[J]. Lancet, 2009, 373(9678):1905-1917.
[11]
Zhao XQ, Chen Y, Yuan YD. Evaluation on value of C-reactive protein, interleukin-8 in acute exacerbation of asthma[J]. Clin Focus, 2009, 24(14):1217-1220.
Shi L, Wang L, Wang B, et al. Regulatory mechanisms of betacellulin in CXCL8 production from lung cancer cells[J]. J Transl Med, 2014, 12:70.
[14]
Mereado N, To Y, Kobayashi Y, et al. p38 mitogen-activated protein kinase-γ inhibition by long-acting β2 adrenergic agonists reversed steroid insensitivity in severe asthma[J]. Mol Pharmacol, 2011, 80(6):1128-1135.
[15]
Qiao J, Li A, Jin X, et al. Mastic alleviates allergic Inflammation in asthmatic model mice by inhibiting recruitment of eosinophils[J]. Am J Respire Cell Mol Biol, 2011, 45(1):95- 100.
[16]
Barnes PJ. Role of HDAC2 in the Pathophysiology of COPD[J]. Annu Rev Physiol, 2009, 71:451-464.
[17]
Grausenburger R, Bilic I, Boucheron N, et al. Conditional deletion of histone deacetylase 1 in T cells leads to enhanced airway inflammation and increased Th2 cytokine production[J]. J Immunol, 2010, 185(6):3489-3497.
[18]
Li CY, Peng J, Ren LP, et al. Roles of histone hypoacetylation in LAT expression on T cells and Th2 polarization in allergic asthma[J]. J Transl Med, 2013, 30(11):26.
[19]
Zhao L, Chen CN, Hajji N, et al. Histone deacetylation inhibition in pulmonary hypertension:therapeutic potential of valproic acid and suberoylanilide hydroxamic acid[J]. Circulation, 2012, 126(4):455-467.
[20]
Batra S, Balamayooran G, Sahoo MK. Nuclear Factor-κB:a key regulator in health and disease of lungs[J]. J Arch Immunol Ther Exp, 2011(59):335-351.
