Effect of clarithromycin on expressions of HDAC2and GR in smoke-exposed asthmatic mice
10.7652/jdyxb201705013
- VernacularTitle:克拉霉素对激素反应性通路中组蛋白去乙酰化酶2及糖皮质激素受体的影响
- Author:
Shuyu SHANG
;
Wei QU
;
Yonghua LIU
- Keywords:
clarithromycin;
smoke exposure;
asthma;
inflammation;
histone deacetylase 2;
glucocorticoid receptor
- From:
Journal of Xi'an Jiaotong University(Medical Sciences)
2017;38(5):688-692,719
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of clarithromycin on the expressions of histone deacetylase-2 (HDAC2) and glucocorticoid receptor (GR) of cigarette smoke-exposed asthmatic mice.Methods BALB/c mice were chosen to be the subjects of this study.They were raised to establish asthma model (OVA group);and mice in one asthma group were exposed to smoke (SEA group), one asthma group were treated with clarithromycin (CAM group) after smoke exposure.Control group mice were used as parallel comparison.The histopathological changes were studied to assess lung tissue inflammation.Cell counts in bronchoalveolar lavage fluid were also tested for airway inflammation.Histone deacelytase2 (HDAC2) activity of lung tissues was measured by qRT-PCR.HDAC2 and GR expressions in the lung tissue were detected by Western blot.Results Histopathologic observation showed massive infiltration of inflammatory cells in both OVA group and SEA group, while inflammation infiltration attenuated in CAM group.Compared with those in CAM group, the levels of IL-4 and IL-8 in bronchoalveolar lavage fluid of SEA group increased significantly (104.36±14.39 vs.65.49±10.82, 681.35±66.18 vs.321.49±90.37;P=0.031, 0.017).The expression of HDAC2 mRNA in CAM group was significantly higher than that in SEA group (0.062±0.013 vs.0.031±0.015, P=0.032).The expressions of HDAC2 protein (0.23±0.017 vs.0.49±0.022, P=0.033) and GR protein (0.19±0.014 vs.0.64±0.023, P=0.011) were significantly lower in SEA group than in CAM group.Conclusion Clarithromycin could attenuate airway inflammation in smoke-exposed asthmatic mice.The mechanism of action may be related to the expression of HDAC2 gene in the lower reaches by combining with GR.
