The effects of propofol on the lipopolysaccharide induced activation of mitogen-activated protein kinase pathway in humanmononuc lear macrophage cells

Abstract

Objective To study the effects of propofol on the lipopolysaccharide induced activation of mitogen-activated protein kinase(MAPK) pathway in human mononuclear macrophage cells(THP-1).Methods Cultured THP-1 cells were randomly divided into four groups:intralipid(the solvent for propofol,20 mg/L) group (C group),lipopolysaccharide(LPS) (10 mg/L) group (L group),propofol(20 mg/L) group (P group),propofol(20 mg/L) and LPS(10 mg/L) group (P+L group).The phosphorylation of p38MAPK,extracellular-signal regulated protein kinase (ERK)1/2 and c-Jun amino-terminal kinase (JNK)1/2 were detected by western blot assay at 0.5,1,2 h and 6 h after LPS or propofol treatment.Results Compared with C group,the level of pp38MAPK(relative intensity:14.67±0.82),p-ERK1/2(relative intensity:1.34±0.05) and p-JNK1/2(relative intensity:4.49±0.51 )increased dramatically in L group at 0.5 h after LPS treatment (P＜0.05).Compared with C group,the level of p-p38MAPK(relative intensity:11.78±0.75),p-ERK1/2(relative intensity:0.58±0.05) and p-JNK1/2(relative intensity:3.31±0.55) in L group increased significantly at 1 h after LPS treatment(P＜0.05).However,the phosphorylation level of p-ERK1/2(relative intensity:0.14+0.02)in P+L group was significantly lower than that of L group at 1 h.After LPS treatment 2 h,compared with C group the level of p-p38MAPK(relative intensity:15.60±0.96) and p-JNK1/2(relative intensity:8.33±0.70) in L group increased obviously(P＜0.05),but compared with L group,the level of p-p38MAPK (relative intensity:4.52±0.23),p-JNK1/2 (relative intensity:1.80±0.70)decreased dramatically in P+L group(P＜0.05).After LPS treatment 6 h,the level of p-p38MAPK(relative intensity:18.89±1.22) and p-JNK1/2 (relative intensity:2.58±0.50) increased significantly in L goup (P＜0.05) compared with C group,however,the phosphorylation level of p38MAPK (relative intensity:3.91±0.30) in P+L group was obviously lower than that of L group (P＜0.05).Conclusions In THP-1 cells,LPS can induce the phosphorylation of p38MAPK,ERK1/2 and JNK1/2,however,this effect can be partial inhibited by propofol,with might be the potential mechanism in anti-inflammation effect. Key words: Propofol; Lipopolysaccharide; Human mononuclear macrophage cell; mitogen-activated protein kinase pathway; Phosphorylation