title: Regulation of neutrophil-mediated killing of Staphylococcus aureus and chemotaxis by c-jun NH2 terminal kinase.
abstract: The role of JNK in neutrophil chemotaxis and killing of microbial pathogens remains unclear. Using a recently described cell-permeable peptide inhibitor of the JNK pathway, based on the JBD of JIP-1, coupled to the protein transduction domain of HIV-TAT (TAT-JIP), in association with control peptides, we demonstrate that the JNK pathway plays a major role in regulating human neutrophil chemotaxis and killing of microbial pathogens. Serum-opsonized Staphylococcus aureus elicited JNK activation and c-jun phosphorylation. The activation of the JNK pathway and bactericidal activity were inhibited by the TAT-JIP peptide. The stimulation of oxygen radical generation by S. aureus was dependent on the JNK signaling pathway, as was the phagocytosis of serum-opsonized bacteria. Chemotaxis to activated serum complement but not random migration was inhibited by the TAT-JIP peptide. The findings demonstrate a major role for the JNK signaling pathway in neutrophil-mediated defense against microbial pathogens.
authors.affiliation: Department of Immunopathology, Children, Youth and Women's Health Service, North Adelaide, South Australia, Australia.
authors.forename: Mei-Chun
authors.initials: MC
authors.lastname: Yeh
authors.forename: Violet
authors.initials: V
authors.lastname: Mukaro
authors.forename: Charles S
authors.initials: CS
authors.lastname: Hii
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferrante
mesh_terms: D015153:Blotting, Western; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D004791:Enzyme Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases