Differential requirement for c-Jun N-terminal kinase 1 in lung inflammation and host defense

• Published in: PloS one 2012-04, Vol.7 (4), p.e34638-e34638
• Main Authors: Van der Velden, Jos, Janssen-Heininger, Yvonne M W, Mandalapu, Sivanarayna, Scheller, Erich V, Kolls, Jay K, Alcorn, John F
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animal tissues; Animals; Antimicrobial peptides; Apoptosis; Biology; c-Jun protein; Cascades; Cells, Cultured; Chemokines; Children & youth; Clonal deletion; Cytokines; E coli; Epithelial cells; Escherichia coli; Families & family life; Health aspects; Histochemistry; Histopathology; Immune clearance; Immunity; Infections; Inflammation; Influenza; Influenza A; Interleukin 17; Interleukin-17 - metabolism; JNK protein; Kinases; Ligands; Lung - immunology; Lung - metabolism; Lung - microbiology; Lung diseases; Lungs; Lymphocytes; Medicine; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 8 - metabolism; Morbidity; Pathogenesis; Pathogens; Pediatrics; Peptides; Phosphorylation; Pneumonia; Pneumonia - metabolism; Rodents; Signal transduction; Signal Transduction - physiology; Signaling; Staphylococcus aureus; Staphylococcus aureus - pathogenicity; Studies; Therapeutic applications; Transcription factors; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0034638

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.