Effects and mechanism of methionine restriction on macrophage for lipopolysaccharide-induced acute lung injury in mice

Abstract

Objective To investigate the effects of methionine restriction (MR) on macrophages in lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to explore the underlying mechanism. Methods According to the random number table method, 36 male C57BL/6J mice (6~8 weeks old, 23±2 g) were divided into 3 groups with 12 mice in each group: the sham group, the LPS group and the LPS+MR group. HE staining and pathological scoring of lung injury were performed in lung tissues. The expression of LPS-binding protein (LBP) and Toll-like receptor-4 (TLR4) was detected by RT-qPCR and Western blotting. Macrophage-colony stimulating factor (M-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF) and chemokine C-C motif ligand 3(CCL3) which are all macrophage-associated chemokines were analyzed by immunohistochemistry. Results Compared with the sham group, the pathological score of lung injury in the LPS group was significantly increased (P < 0.01);The mRNA and protein expression levels of LBP and TLR4 were significantly increased; The number of positive cells of CD11b, F4/80, M-CSF, GM-CSF and CCL3 were significantly increased (P < 0.01). MR significantly improved LPS-induced ALI, and decreased the pathological score of lung injury (P < 0.01); The mRNA and protein expression levels of LBP and TLR4 were decreased; Compared with the LPS group, the number of positive cells of CD11b, F4/80, M-CSF, GM-CSF and CCL3 were reduced in the LPS+MR group (P < 0.01). Conclusion MR could attenuate LPS-induced ALI by inhibiting the expression of macrophage chemokines and preventing infiltration and activation of macrophage to lungs.

Keywords

• acute lung injury
• macrophage
• methionine restriction
• chemokines
• lipopolysaccharide