title: The differential interaction of p38 MAP kinase and tumor necrosis factor-alpha in human alveolar macrophages and monocytes induced by Mycobacterium tuberculois.
abstract: Cellular signaling by TNF-alpha 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-alpha activity. Here, we compared the activation and mutual regulation of p38 MAP kinase and TNF-alpha 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-alpha mRNA was assessed by real-time RT-PCR, and TNF-alpha 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-alpha mRNA and protein. Activation of ERK (1/2) by MTB followed similar kinetics in both AM and MN. TNF-alpha 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-alpha expression.
authors.affiliation: Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Surewicz
authors.forename: Htin
authors.initials: H
authors.lastname: Aung
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kanost
authors.forename: Leola
authors.initials: L
authors.lastname: Jones
authors.forename: Rana
authors.initials: R
authors.lastname: Hejal
authors.forename: Zahra
authors.initials: Z
authors.lastname: Toossi
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D016676:Macrophages, Alveolar / Q000201:enzymology* / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases