PAF-induced RANTES production by human airway smooth muscle tells requiresboth p38 MAP kinase and Erk

Airway smooth muscle (ASM) cells, which have been regarded as having contra ctile properties in response to contractile inflammatory mediators, may als o participate in airway inflammatory response by expressing various cytokin es, including RANTES. However, the intracellular signal that regulates cyto kine expression in ASM cells has not been determined. In the present study, we examined the role of p38 mitogen-activated protein (MAP) kinase and ext racellular signal-regulated kinase (Erk) in RANTES production by ASM cells stimulated by platelet-activating factor (PAF) and tumor necrosis factor (T NF)-alpha. The results showed that PAF induced the threonine and tyrosine p hosphorylation of p38 MAP kinase and Erk, and p38 MAP kinase and Erk activi ty. SE 203580 and PD 98059 almost completely inhibited p38 MAP kinase and E rk activity, respectively. SE 203580 and PD 98059 partially inhibited and a cted additively to inhibit PAF-induced RANTES production. PAF also induced c-jun-NH2-terminal kinase (JNK) phosphorylation. TNF-alpha induced p38 MAP kinase and Erk phosphorylation, but neither SB 203580 nor PD 98059 inhibite d RANTES production. These results indicate that both p38 MAP kinase and Er k involve RANTES production by ASM cells stimulated with PAF, but not TNF-a lpha and that the role of p38 MAP kinase and Erk in RANTES production by AS M cells appears to be stimulus-dependent.