Therapeutic effects of histone deacetylase inhibitor givinostat on air inflammation and high airway resistance in a murine asthma model
10.3760/cma.j.issn.0578-1426.2017.02.008
- VernacularTitle:组蛋白去乙酰化酶抑制剂 givinostat 对支气管哮喘小鼠气道炎症和气道高阻力的干预作用
- Author:
Xinming SU
;
Yuan REN
;
Lingfei KONG
;
Jian KANG
- Keywords:
Asthma;
Histone deacetylase inhibitor;
Inflammation;
Airway resistance
- From:
Chinese Journal of Internal Medicine
2017;56(2):121-126
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effects of givinostat , a histone deacetylase inhibitor (HDACI), on the development of chronic asthma with airway inflammation , airway remodeling and airway hyperresponsiveness ( AHR) .Methods BALB/C mice were randomly divided into control group , asthma group, dexamethasone group and givinostat group (n=12 per group).AHR was assessed.Total cell numbers and differential counts , interleukin-4 ( IL-4 ) , interleukin-5 ( IL-5 ) and interferon-γ( IFNγ) levels in the bronchoalveolar lavage fluid ( BALF) were measured in the above 4 groups.The pathology of lung tissue was evaluated .Immunohistochemical ( IHC) staining and Western blot were used to detect αsmooth muscle actin(α-SMA) and transforming growth factor-β1(TGFβ1).Results Compared with the asthma only group, givinostat treatment relieved airway resistance (2.96 ±1.01 vs 6.50 ±0.79,P<0.05).Total inflammatory cells [(33.04 ±5.62) ×104/ml vs (98.04 ±9.27) ×104/ml,P<0.01], eosinophil cells [(9.17 ±2.33) ×104/ml vs(37.64 ±6.98) ×104/ml, P <0.01], IL-4 [(10.12 ±2.98)ng/ml vs (16.88 ±2.78)ng/ml,P<0.05] and IL-5 [(27.09 ±3.62)ng/ml vs (37.86 ±7.34)ng/ml, P<0.05] levels were all reduced in givinostat group , while IFNγ[ ( 91.86 ±23.73 ) pg/ml vs ( 60.49 ±11.88 ) pg/ml, P>0.05] was enhanced in BALF.Inflammatory cell infiltration around the airway was reduced , with decreased inflammatory cell score [(1.60 ±0.69) points vs (3.40 ±0.68) points, P <0.01] and inflammatory cell number (111.65 ±31.41 vs 601.25 ±186.85, P<0.01).The goblet cell metaplasia [(26.36 ±2.33)%vs (57.21 ±11.56)%] and collagen deposition area [(52.77 ±7.58)μm2/μm vs (111.81 ±12.40)μm2/μm] were obviously reduced (P<0.01).The expressions of α-SMA and TGFβ1 in the lung tissue were both significantly decreased ( P<0.01 ) .Conclusion Givinostat treatment can reduce airway inflammation , airway remodeling and airway hyperresponsiveness in chronic asthma .Its effect is comparable to that of glucocorticoid hormone treatment .
