Jm. Ayala et al., Serum-induced monocyte differentiation and monocyte chemotaxis are regulated by the p38 MAP kinase signal transduction pathway, J LEUK BIOL, 67(6), 2000, pp. 869-875
Regulation by the p38 mitogen-activated protein (MAP) kinase signaling path
way of monocytic inflammatory functions was evaluated using L-790,070, a po
tent and selective inhibitor of p38 MAP kinase, Three major functions of mo
nocytes 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 prote
in-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-i
nduced chemotaxis in a concentration-dependent manner with an IC50 of 0.3 n
M, However, the ability of serum-derived macrophages to phagocytose apoptot
ic neutrophils was unaffected by L-790,070, The concentration with which L-
790,070 inhibited both differentiation and chemotaxis was similar to that n
ecessary 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 diffe
rentiation and prevented chemotaxis was by inhibiting p38 MAP kinase activi
ty.