Borrelia burgdorferi-Induced Expression of Matrix Metalloproteinases from Human Chondrocytes Requires Mitogen-Activated Protein Kinase and Janus Kinase/Signal Transducer and Activator of Transcription Signaling Pathways
| Autor: | Cheleste M. Thorpe, Aruna K. Behera, Linden T. Hu, Ethan Hildebrand, Wendy E. Smith, J. Michael Kidder |
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| Rok vydání: | 2004 |
| Předmět: |
STAT3 Transcription Factor
MAPK/ERK pathway MAP Kinase Signaling System Immunology p38 Mitogen-Activated Protein Kinases Microbiology Chondrocytes Humans Borrelia burgdorferi Protein kinase A Cells Cultured Cellular Microbiology: Pathogen-Host Cell Molecular Interactions MAP kinase kinase kinase biology Kinase biology.organism_classification Molecular biology DNA-Binding Proteins Enzyme Activation Infectious Diseases Trans-Activators STAT protein Matrix Metalloproteinase 3 Parasitology Matrix Metalloproteinase 1 Mitogen-Activated Protein Kinases Signal transduction STAT6 Transcription Factor Janus kinase |
| Zdroj: | Infection and Immunity. 72:2864-2871 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.72.5.2864-2871.2004 |
| Popis: | Elevations in matrix metalloproteinase 1 (MMP-1) and MMP-3 have been found in patients with Lyme arthritis and in in vitro models of Lyme arthritis using cartilage explants and chondrocytes. The pathways by whichB. burgdorferi, the causative agent of Lyme disease, induces the production of MMP-1 and MMP-3 have not been elucidated. We examined the role of the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways in MMP induction byB. burgdorferi. Infection withB. burgdorferiresults in rapid phosphorylation of p38 and JNK within 15 to 30 min. Inhibition of JNK and p38 MAPK significantly reducedB. burgdorferi-induced MMP-1 and MMP-3 expression. Inhibition of ERK1/2 completely inhibited the expression of MMP-3 in human chondrocytes followingB. burgdorferiinfection but had little effect on the expression of MMP-1.B. burgdorferiinfection also induced phosphorylation and nuclear translocation of STAT-3 and STAT-6 in primary human chondrocytes. Expression of MMP-1 and MMP-3 was significantly inhibited by inhibition of JAK3 activity. Induction of MMP-1 and -3 following MAPK and JAK/STAT activation was cycloheximide sensitive, suggesting synthesis of intermediary proteins is required. Inhibition of tumor necrosis factor alpha (TNF-α) significantly reduced MMP-1 but not MMP-3 expression fromB. burgdorferi-infected cells; inhibition of interleukin-1β (IL-1β) had no effect. Treatment ofB. burgdorferi-infected cells with JAK and MAPK inhibitors significantly inhibited TNF-α induction, consistent with at least a partial role for TNF-α inB. burgdorferi-induced MMP-1 expression in chondrocytes. |
| Databáze: | OpenAIRE |
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