title: Selective activation of p38 mitogen-activated protein kinase cascade in human neutrophils stimulated by IL-1beta.
abstract: We investigated activation of mitogen-activated protein kinase (MAPK) subtype cascades in human neutrophils stimulated by IL-1beta. IL-1beta induced phosphorylation and activation of p38 MAPK and phosphorylation of MAPK kinase-3/6 (MKK3/6). Maximal activation of p38 MAPK was obtained by stimulation of cells with 300 U/ml IL-1beta for 10 min. Extracellular signal-regulated kinase (ERK) was faintly phosphorylated and c-Jun N-terminal kinase (JNK) was not phosphorylated by IL-1beta. IL-1beta primed neutrophils for enhanced release of superoxide (O(2)(-)) stimulated by FMLP in parallel with increased phosphorylation of p38 MAPK. IL-1beta also induced O(2)(-) release and up-regulation of CD11b and CD15, and both responses were inhibited by SB203580 (p38 MAPK inhibitor), suggesting that p38 MAPK activation mediates IL-1beta-induced O(2)(-) release and up-regulation of CD11b and CD15. Combined stimulation of neutrophils with IL-1beta and G-CSF, a selective activator of the ERK cascade, resulted in the additive effects when the priming effect and phosphorylation of p38 MAPK and ERK were assessed. IL-1beta induced phosphorylation of ERK and JNK as well as p38 MAPK in human endothelial cells. These findings suggest that 1) in human neutrophils the MKK3/6-p38 MAPK cascade is selectively activated by IL-1beta and activation of this cascade mediates IL-1beta-induced O(2)(-) release and up-regulation of CD11b and CD15, and 2) the IL-1R-p38 MAPK pathway and the G-CSF receptor-ERK pathway work independently for activation of neutrophils.
authors.affiliation: Department of Physiology, Osaka City University Medical School, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Hino
authors.forename: H
authors.initials: H
authors.lastname: Kutsuna
authors.forename: F
authors.initials: F
authors.lastname: Hato
authors.forename: C
authors.initials: C
authors.lastname: Sakamoto
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Tatsumi
authors.forename: S
authors.initials: S
authors.lastname: Kitagawa
mesh_terms: D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D016256:Lewis X Antigen / Q000096:biosynthesis; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; D020935:MAP Kinase Signaling System; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D007375:Interleukin-1; D016256:Lewis X Antigen; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; C482530:MAP2K3 protein, human; C482566:MAP2K6 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases