Role of calcineurin in airway remodeling in the rats with bronchial asthma

Abstract

Objective To investigate the expreession and activity of calcineurin(CaN) in asthmatic rat lungs,and to explore the role of CaN in airway remodeling with asthma. Methods Twenty Wistar rats were randomly divided into two groups:the control group and the asthma group, 10 rats each group. The rats were sensitized and challenged with ovalbumin to establish the asthmatic model, so did the rats in control group with saline instead. The following parameters were measured:airway inflammation by HE staining, the bronchial wall thickness by computer-assisted image analysis system; the expression of CaNmRNA by Real-time PCR, the protein expression of CaN by immunohistochemistry and the activity of CaN by biochemical method;the cell cycle distribution of monocyte in peripheral blood by flow cytometry and the level of IL-4 and TNF-α by ELISA. Results ①The bronchial wall thickness of the asthma group was significantly increased compared with that of the control group ( P ＜ 0. 01 ). ②The expression of CaNmRNA,the protein expression of CaN and the activity of CaN in the asthma group were significantly higher than those of the control group( P ＜0.05, P ＜0. 01, P ＜0. 01 ,respectively). ③The level of IL-4and TNF-α in plasma of asthma group was significantly higher than that in control group ( P ＜0.01, P ＜0. 05 , respectively). ④When compared with the control group, the percentage of monocyte in the G0/G1phase was lower in the asthma group. Howover,the percentage of monocyte in the S phase and S+ G2/M phase was significantly higher (all P ＜0.01). ⑤There was a positive correlation between the activity of CaN in rat lungs and the percentage of monocyte in the S phase and S+G2/M phase in peripheral blood (all P ＜0.05) ,the same between the activity of CaN and the level of IL-4 in plasma or the bronchial wall thickness( P ＜0.05, P ＜0. 01, respectively). There was a positive correlation between the level of IL-4and the level of TNF-αin plasma( P ＜0.05) ,and so between the level of IL-4 in plasma and the bronchial wall thickness ( P ＜0.05). Conclusions The activity of CaN in asthmatic rat lungs was increased and the rising of it might play an important part in the development of airway remodeling in asthma by promoting the monocyte division and hyperplasia,or even causing the producing of IL-4 or TNF-α. Key words: Asthma; Calcineurin; Airway remodeling