Effect of cigarette smoke exposure on the expression of CCR7 and levels of Th1/Th2 cytokines in asthmatic rats

Abstract

Objective: To investigate the effect of cigarette smoke exposure on the expression of CC Chemokine receptor 7 (CCR7) and levels of Th1/Th2 cytokines in asthmatic rats. Methods: Forty Wistar rats were randomly divided into four groups: control group, asthma group, smoke exposure group, asthma-smoke exposure group. The asthma group were sensitized with ovalbumin (OVA) and Aluminum hydroxide at day 1, 8 and challenged with OVA at day 15 by atomization for 8 weeks.While control group was sensitized and challenged with normal saline instead of OVA.The smoke exposure group was sensitized and challenged with normal saline instead of OVA followed passive smoking for 8 weeks. The asthma-smoke exposure group was challenged with OVA followed passive smoking. The pathological changes of different groups were observed by HE-staining. CCR7 was semiquantitatively analyzed in lungs by immunohistochemistry.The concentration of CC chemokine ligand (CCL)19, CCL21, interferon (IFN)-γ and interleukin (IL)-4 in peripheral blood and CCL19 and CCL21 in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent (ELESA) assay. Results: In asthma group, smoke exposure group and asthma-smoke exposure group, the various degrees of inflammatory reaction appeared in lung tissue and the asthma-smoke exposure group was with the most significant reaction. In the lung tissues of the rats from asthma group, smoke exposure group and asthma-smoke exposure group, the average optical density (AOD) of CCR7 were significantly higher than those in control group (0.350±0.023, 0.252±0.022, 0.400±0.029 vs 0.180±0.020, all P<0.01). The AOD of CCR7 of asthma-smoke exposure group was much higher than both that in asthma group and in smoke exposure group (both P<0.01). In asthma group, smoke exposure group and asthma-smoke exposure group, the concentrations of both CCL19 and CCL21 in peripheral blood and BALF were significantly higher than that in control group (all P<0.01). The concentrations of both CCL19 and CCL21 in peripheral blood and BALF of asthma-smoke exposure group were significantly higher than the results in asthma group and in smoke exposure group (all P<0.01). The concentrations of IFN-γ in peripheral blood of asthma group and asthma-smoke exposure group were lower than those in control group [(33±3), (17±3) vs (70±4) pg/ml], but asthma-smoke exposure group was much lower than the results in asthma group (all P<0.01). The concentration of IFN-γ in peripheral blood of smoke exposure group[(100±5)pg/ml]was higher than that in control group and asthma-smoke exposure group (both P<0.01). In asthma group, smoke exposure group, asthma-smoke exposure group, the concentrations of IL-4 in peripheral blood were significantly higher than those in control group [(54±4), (42±4), (76±4) vs (30±4) pg/ml, all P<0.01]. The concentrations of IL-4 in peripheral blood of asthma-smoke exposure group was significantly higher than those in asthma group and in smoke exposure group (both P<0.01). Conclusion: Cigarette smoke could enhance the expression of CCR7 and its ligand, and it can also result in exacerbations of asthma by reducing the expression level of IFN-γ (the representative of Th1 cytokine) and increasing the expression level of IL-4 (the representative of Th2 cytokine).