title: Differential requirement for c-Jun N-terminal kinase 1 in lung inflammation and host defense.
abstract: The c-Jun N-terminal kinase (JNK) - 1 pathway has been implicated in the cellular response to stress in many tissues and models. JNK1 is known to play a role in a variety of signaling cascades, including those involved in lung disease pathogenesis. Recently, a role for JNK1 signaling in immune cell function has emerged. The goal of the present study was to determine the role of JNK1 in host defense against both bacterial and viral pneumonia, as well as the impact of JNK1 signaling on IL-17 mediated immunity. Wild type (WT) and JNK1 -/- mice were challenged with Escherichia coli, Staphylococcus aureus, or Influenza A. In addition, WT and JNK1 -/- mice and epithelial cells were stimulated with IL-17A. The impact of JNK1 deletion on pathogen clearance, inflammation, and histopathology was assessed. JNK1 was required for clearance of E. coli, inflammatory cell recruitment, and cytokine production. Interestingly, JNK1 deletion had only a small impact on the host response to S. aureus. JNK1 -/- mice had decreased Influenza A burden in viral pneumonia, yet displayed worsened morbidity. Finally, JNK1 was required for IL-17A mediated induction of inflammatory cytokines and antimicrobial peptides both in epithelial cells and the lung. These data identify JNK1 as an important signaling molecule in host defense and demonstrate a pathogen specific role in disease. Manipulation of the JNK1 pathway may represent a novel therapeutic target in pneumonia.
authors.affiliation: Department of Pathology, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Jos
authors.initials: J
authors.lastname: Van der Velden
authors.forename: Yvonne M W
authors.initials: YM
authors.lastname: Janssen-Heininger
authors.forename: Sivanarayna
authors.initials: S
authors.lastname: Mandalapu
authors.forename: Erich V
authors.initials: EV
authors.lastname: Scheller
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: John F
authors.initials: JF
authors.lastname: Alcorn
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020381:Interleukin-17 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D011014:Pneumonia / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013211:Staphylococcus aureus / Q000472:pathogenicity
chemical_list: D020381:Interleukin-17; D048055:Mitogen-Activated Protein Kinase 8