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

Abstract

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 μg 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)-1β, IL-6, tumour necrosis factor (TNF)-α, 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-1β, IL-6, and TNF-α were markedly higher. Treatment with colchicine reduced the levels of IL-1β, IL-6, and TNF-α 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-1β, IL-6, and TNF-α 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.