Serum-induced monocyte differentiation and monocyte chemotaxis are regulated by the p38 MAP kinase signal transduction pathway
Serum-induced monocyte differentiation and monocyte chemotaxis are regulated by the p38 MAP kinase signal transduction pathway
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DOI：
10.1002/jlb.67.6.869
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发表时间：
2000-06-01
影响因子：
5.5
通讯作者：
Hanlon, WA
中科院分区：
文献类型：
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作者：
Ayala, JM;Goyal, S;Hanlon, WA
为探讨p38丝裂原活化蛋白(MAP)信号通路对单核细胞炎症功能的调节作用，用p38丝裂原活化蛋白(MAP)激酶的抑制剂L-790,070对单核细胞的分化、趋化和吞噬功能进行了研究，L-790,070抑制血清诱导的单核细胞分化，IC50为0.5 nM，RANTES诱导的单核细胞趋化作用，巨噬细胞炎症蛋白-1α(MIP-1α)，单核细胞趋化蛋白-1和单核细胞趋化蛋白-1(FMLP)对L-790,070均敏感。L-790,070以浓度依赖的方式抑制单核细胞趋化蛋白-1诱导的趋化作用，IC50为0.3 nM，而L-790,070对血清来源的巨噬细胞吞噬凋亡中性粒细胞的能力无影响，其抑制分化和趋化作用与抑制脂多糖刺激下MAPKAP激酶(0.3 nM)的p38 MAPK激活所需的浓度相似。因此，本报告中的数据提示，L-790,070阻断单核细胞分化和阻止趋化的机制是通过抑制p38 MAPK活性而实现的。
Regulation by the p38 mitogen-activated protein (MAP) kinase signaling pathway of monocytic inflammatory functions was evaluated using L-790,070, a potent and selective inhibitor of p38 MAP kinase, Three major functions of monocytes were investigated: differentiation, chemotaxis, and phagocytosis, L-790,070 inhibited serum-induced monocyte differentiation with an IC50 of 0.5 nM, Monocyte chemotaxis induced by RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alpha), monocyte chemotactic protein-1 (MCP-1), and fMLP were all sensitive to L-790,070, When titrated, L-790,070 inhibited MCP-1-induced chemotaxis in a concentration-dependent manner with an IC50 of 0.3 nM, However, the ability of serum-derived macrophages to phagocytose apoptotic neutrophils was unaffected by L-790,070, The concentration with which L-790,070 inhibited both differentiation and chemotaxis was similar to that necessary to inhibit p38 MAP kinase activation of MAPKAP kinase (0.3 nM) in response to stimulation by lipopolysaccharide. Therefore, the data in this report suggest that the mechanism by which L-790,070 blocked monocyte differentiation and prevented chemotaxis was by inhibiting p38 MAP kinase activity.