Yeh, M.Mukaro, V.Hii, C.Ferrante, A.2011-02-082011-02-082010Journal of Leukocyte Biology, 2010; 87(5):925-9321938-36731938-3673http://hdl.handle.net/2440/62411The 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.en© Society for Leukocyte BiologyNeutrophilsHL-60 CellsHumansStaphylococcus aureusStaphylococcal InfectionsJNK Mitogen-Activated Protein KinasesEnzyme InhibitorsBlotting, WesternImmunoprecipitationChemotaxis, LeukocytePhagocytosisJournal article002009777210.1189/jlb.06093990002793550000192-s2.0-7795252834734171Hii, C. [0000-0002-7107-8935]Ferrante, A. [0000-0002-2581-6407]