Effects of smoking on expressions of HIF-1α and HDAC2 in asthmatic mice

Abstract

To explore the effects of smoking on airway inflammation through the expressions of hypoxia-inducible factor-1α (HIF-1α) and histone deacetylase-2 (HDAC2) in asthmatic mice. A total of 30 female SPF BALB/c mice were divided randomly into 3 groups of control (C), asthma (A) and smoking asthma (S). The latter two groups were sensitized and challenged with ovalbumin (OVA) for asthmatic modeling. The mice of group S were placed into a self-made fumigating box for passive smoking. While group S was sensitized and challenged with normal saline instead of OVA. The pathological changes of different groups were observed. The different cell counts of bronchoalveolar fluid (BALF) were analyzed. The expressions of HIF-1α and HDAC2 were detected by immunohistochemistry. The level of interleukin (IL)-8 in BALF was detected by enzyme-linked immunosorbent assay (ELISA). And the levels of HIF-1α and HDAC2 in lung homogenate were measured by Western blot. The ratios of eosinophil (EOS) to total cell numbers of BALF in groups A and S were significantly higher than that in group C ((8.90 ± 1.60)%, (7.52 ± 0.63)% vs (0.60 ± 0.10)%, both P < 0.01), while the ratio of neutrophile (NEU) in group S was higher than that in group A ((18.24 ± 5.19)% vs (8.46 ± 1.58)%, P < 0.01). Western blot showed that HIF-1α expressions in lung homogenate of groups A and S were significantly elevated than that in groups C (0.144 ± 0.008, 0.238 ± 0.015 vs 0.081 ± 0.005, both P < 0.01). While the HIF-1α level of group S was higher than that of group A (P < 0.01). And the expressions of HDAC2 in groups A and S significantly decreased than that in group C (0.287 ± 0.008, 0.164 ± 0.015 vs 0.452 ± 0.041, both P < 0.01). While the HDAC2 level of group S was lower than that of group A (P < 0.01). The BALF level of IL-8 in group S was higher than those in groups A and C ((42.07 ± 4.54) vs (21.66 ± 2.78), (14.33 ± 3.73) pg/ml, both P < 0.01). There were significantly negative correlations between the expressions of HIF-1α and HDAC2 (r = -0.950, P < 0.01) in lung as well as HDAC2 in lung and IL-8 (r = -0.855, P < 0.01) in BALF. Cigarette smoking aggravates the airway inflammation through a down-regulated expression of HDAC2 by activating HIF-1α.