Expression and function of DAPK1 in lung tissues of mouse with acute lung injury

Abstract

Objective To investigate the expression of death associated protein kinase 1(DAPK1) in lung tissues of mouths with LPS induced acute lung injury(ALI) and its function in ALI. Methods Thirty C57 male mice were randomly divided into 5 groups: control group, LPS induced acute lung injury group for 3 h, 6 h, 12 h and 24 h group. Histological changes of the lungs were observed by HE staining; The expression and distribution of DAPK1 in the lung tissues was detected by western blot, qPCR and Immunohistochemistry. The serum levels of TNF-α and IL-6 were detected by ELISA. Six mice were pretreated with 2 mg/kg TC-DAPK 6, a selectivity DAPK1 inhibitor, and then 10 mg/kg LPS was used to induce mice acute lung injury by intraperitoneal injection. The expression of DAPK1 and NF-κB p65 was evaluated using western blot and qPCR, and ELISA was used to analyze the level of serum TNF-α and IL-6. Kaplan-Meier analysis was evaluated the lifespan of these mice. Results The HE stain showed that pathological of lung tissue damage became severe along with time. Immunohistochemistry demonstrated that. The area of DAPK1 protein expression was more large with time increased in LPS group, compared to control group (P<0.05). The level of serum TNF-α and IL-6 was significantly higher than control group (P<0.05). The expression of DAPK1 and NF-κB p65 and serum TNF-α and IL-6 level was significantly decreased after pretreated with TC-DAPK 6 and stimulated with LPS, compared to LPS alone group (P<0.05). Moreover, Kaplan-Meier analysis showed the lifespan of mice by pretreated with TC-DAPK 6 was longer than LPS alone group (P<0.01). Conclusion DAPK1 involved in LPS induced mice acute lung injury by modulation NF-κB p65 and the production and released of inflammation mediator. It might be a potential target for ALI/ARDS treatment. Key words: Death associated protein kinase 1; Acute lung injury; Nuclear factor-κB