Protective Effect of Colchicine on LPS-Induced Lung Injury in Rats via Inhibition of P-38, ERK1/2, and JNK Activation

Introduction: Acute lung injury (ALI), a commonly detected syndrome, is characterized by the accumulation of neutrophils and leucocytes, and inflammation of pulmonary tissues. Objective: The present study was designed to investigate the effect and underlying mechanism of colchicine on LPS-induced lung injury. Methods: The rats were divided randomly into 6 groups of 10 each: normal control, untreated, and 4 colchicine (5, 10, 15, and 20 mg/kg) treatment groups. ALI was induced in rats by the administration of 20 mu g LPS intratracheally. Rats in the normal control and untreated groups were injected normal saline, while those in the treatment groups received 5, 10, 15, and 20 mg/kg doses of colchicine daily for 1 month. ELISA was used for determination of interleukin (IL)-1 beta, IL-6, tumour necrosis factor (TNF)-alpha, superoxide dismutase (SOD), and leucocytes in the rat bronchoalveolar lavage fluid (BALF). The expression of P-38, JNK, and Erk-1/2 was analysed by Western blotting. Results: In LPS-administered TC-1 cells, the levels of IL-1 beta, IL-6, and TNF-alpha were markedly higher. Treatment with colchicine reduced the levels of IL-1 beta, IL-6, and TNF-alpha in LPS-administered TC-1 cells. Colchicine treatment caused a marked reduction in LPS-induced accumulation of inflammatory cells in the rat lungs. The LPS-induced aggregation of leucocytes and neutrophils in the rat BALF was also suppressed markedly on treatment with colchicine. Treatment of the lung injury in rats with colchicine caused a marked decrease in the level of IL-1 beta, IL-6, and TNF-alpha in BALF. The LPS-mediated suppression of SOD in the rat BALF was prevented by treatment with colchicine. Treatment of the rats with colchicine attenuated the LPS-induced activation of P-38, Erk1/2, and JNK in pulmonary tissues. Conclusion: In summary, colchicine treatment prevents LPS-induced lung damage in rats through targeting activation of P-38, ERK1/2, and JNK. Therefore, colchicine may be used for the development of treatment for ALI.