The differential interaction of p38 MAP kinase and tumor necrosis factor-α in human alveolar macrophages and monocytes induced by Mycobacterium tuberculois

Cellular signaling by TNF-α is mediated through activation of mitogen activated protein (MAP) kinases. In particular, p38 MAP kinase is activated in mononuclear phagocytes and may be important in sustaining TNF-α activity. Here, we compared the activation and mutual regulation of p38 MAP kinase and TNF-α by MTB in human alveolar macrophages (AM) and blood monocytes (MN). AM and autologous MN were prepared, and stimulated by MTB at 1:1 (bacteria/cell). MAP kinase activation was assessed by immunoprecipitation and kinase activity. TNF-α mRNA was assessed by real-time RT-PCR, and TNF-α immunoreactivity was assessed by ELISA. MTB-induced p38MAP kinase rapidly in AM as compared to MN, and inhibition of p38 MAP kinase by SB203580 reduced both TNF-α mRNA and protein. Activation of ERK (1/2) by MTB followed similar kinetics in both AM and MN. TNF-α produced by MTB sustained p38 MAP kinase activation in MN only. These data suggest that interaction of resident pulmonary macrophages and the more immature MN with MTB differ with regard to both p38 MAP kinase activation and TNF-α expression.