Interleukin-17-induced gene expression in articular chondrocytes is associated with activation of mitogen-activated protein kinases and NF-kappaB

This study examines intracellular signaling events associated with the activation of chondrocytes by the cytokine interleukin-17 (IL-17). Stimulation of normal human articular chondrocytes with IL-17 induced nitric oxide (NO) production, concomitant with an increase in transcripts and de novo transl...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-10, Vol.273 (42), p.27467-27473
Main Authors: Shalom-Barak, T, Quach, J, Lotz, M
Format: Article
Language:English
Subjects:
Arthritis - etiology
Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cartilage, Articular - cytology
Cartilage, Articular - metabolism
Chondrocytes - cytology
Chondrocytes - metabolism
Dexamethasone - pharmacology
Enzyme Activation
Gene Expression Regulation
Humans
Interleukin-17 - pharmacology
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
NF-kappa B - metabolism
Nitric Oxide - biosynthesis
p38 Mitogen-Activated Protein Kinases
Signal Transduction
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Summary:This study examines intracellular signaling events associated with the activation of chondrocytes by the cytokine interleukin-17 (IL-17). Stimulation of normal human articular chondrocytes with IL-17 induced nitric oxide (NO) production, concomitant with an increase in transcripts and de novo translation products of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) genes. Several other genes associated with inflammation and cartilage degradation, such as IL-1beta, IL-6, and stromelysin, were also up-regulated in IL-17-treated chondrocytes. Among signaling events displaying early response to IL-17 in chondrocytes were the mitogen-activated protein (MAP) kinases ERK1, ERK2, JNK, and p38. DNA binding activity of NF-kappaB was also significantly induced. IL-17 effects on NO release, as well as iNOS, COX-2, and IL-6 protein expression, were inhibited by the anti-inflammatory drug dexamethasone. Importantly, dexamethasone blunted IL-17-dependent activation of MAP kinases, suggesting a mechanistic relationship between these activities and the aforementioned gene expression responses. Similar effects of a lesser extent were observed with the p38-specific inhibitor SB203580. These results suggest that IL-17 activation of chondrocytes is associated with and depends at least in part on the activation of MAP kinases and NF-kappaB.
ISSN:0021-9258