Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Cabanski, M; Steinmüller, M; Marsh, LM; Surdziel, E; Seeger, W; Lohmeyer, J.
PKR regulates TLR2/TLR4-dependent signaling in murine alveolar macrophages.
Am J Respir Cell Mol Biol. 2008; 38(1): 26-31.
Doi: 10.1165/rcmb.2007-0010OC
Web of Science
PubMed
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FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Marsh Leigh
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- Abstract:
- The double-stranded RNA (dsRNA)-activated serine/threonine kinase R (PKR) is well characterized as an essential component of the innate antiviral response. Recently, PKR has been implicated in Toll-like receptor (TLR) signal transduction in response to bacterial cell wall components. Its contribution to pulmonary immunity, however, has not yet been elucidated. In this report we investigated whether PKR is involved in TLR2/TLR4-mediated immune responses of primary alveolar macrophages (AM). We found that both TLR2 (Pam3CSK4) and TLR4 (LPS) ligands induced rapid phosphorylation of PKR. Moreover, this activation was strictly dependent on the functionality of the respective TLR. Pharmacologic inhibition of PKR activity using 2-aminopurine (2-AP) and PKR gene deletion was found to reduce the TLR2/TLR4-induced activation of the JNK signaling pathway (MKK4/JNK/c-Jun), but did not affect p38 and extracellular signal-regulated kinase 1/2 activation. Moreover, inhibition of PKR phosphorylation severely impaired TNF-alpha and IL-6 production by AM in response to LPS and Pam3CSK4. In addition, we found that PKR phosphorylation plays a major role in LPS- but not Pam3CSK4-induced activation of the p65 subunit of NF-kappaB. Collectively, these results indicate that functional PKR is critically involved in inflammatory responses of primary AM to gram-positive as well as gram-negative bacterial cell wall components.
- Find related publications in this database (using NLM MeSH Indexing)
- 2-Aminopurine - pharmacology
- Animals -
- Antimetabolites - pharmacology
- Bacteria - immunology
- Cell Wall - immunology
- Cells, Cultured -
- Enzyme Activation - drug effects Enzyme Activation - immunology
- Female -
- Gene Deletion -
- Immunity, Innate - physiology
- Interleukin-6 - biosynthesis Interleukin-6 - genetics Interleukin-6 - immunology
- JNK Mitogen-Activated Protein Kinases - immunology JNK Mitogen-Activated Protein Kinases - metabolism
- Ligands -
- Lipopeptides -
- Lipopolysaccharides -
- Lung -
- MAP Kinase Kinase 4 - genetics MAP Kinase Kinase 4 - immunology MAP Kinase Kinase 4 - metabolism
- MAP Kinase Signaling System - immunology
- Macrophages, Alveolar - immunology Macrophages, Alveolar - metabolism
- Male -
- Mice -
- Mice, Inbred BALB C -
- Mice, Knockout -
- Peptides - pharmacology
- Phosphorylation - drug effects
- Toll-Like Receptor 2 - agonists Toll-Like Receptor 2 - genetics Toll-Like Receptor 2 - immunology Toll-Like Receptor 2 - metabolism
- Toll-Like Receptor 4 - agonists Toll-Like Receptor 4 - genetics Toll-Like Receptor 4 - immunology Toll-Like Receptor 4 - metabolism
- Transcription Factor RelA - genetics Transcription Factor RelA - immunology Transcription Factor RelA - metabolism
- Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - immunology
- eIF-2 Kinase - genetics eIF-2 Kinase - immunology eIF-2 Kinase - metabolism
- p38 Mitogen-Activated Protein Kinases - genetics p38 Mitogen-Activated Protein Kinases - immunology p38 Mitogen-Activated Protein Kinases - metabolism
- Find related publications in this database (Keywords)
- PKR
- 2-aminopurine
- alveolar macrophages
- LPS
- Pam3CSK4