Abstract
Interleukin-1ß is a pro-inflammatory cytokine that causes anti-anabolic and catabolic effects on articular chondrocytes via four major signaling pathways. In this study, we investigated the role of these pathways for the repression of collagen type II, and induction of MMP-1 and -13 by Il-1ß. Human adult chondrocytes were stimulated with IL-1β together with selective inhibitors of the ERK, JNK, p38, and NFκB pathways. Inhibitors of ERK and NFκB could significantly block the induction of MMP-1 and -13 (p<0.05) and the repression of collagen type II (p<0.01). The inhibitor for p38 MAPK was able to block partially MMP-1 and -13 up-regulation (p<0.01), but did not significantly inhibit collagen type II repression. Our data suggest that ERK and NFkB pathways are particularly important for IL-1β regulating collagen type II and MMP-1 and -13 expression and that p38, but not JNK is additionally involved in MMP-1 and -13 induction.
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Acknowledgments
We are grateful for the expert technical assistance by Ms. Anke Nehlen. Supported by the Federal Ministry of Education and Research (BMBF) and the Interdisciplinary Center of Clinical Research (IZKF) of the University Hospital of the University of Erlangen-Nürnberg.
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Fan, Z., Yang, H., Bau, B. et al. Role of mitogen-activated protein kinases and NFκB on IL-1β-induced effects on collagen type II, MMP-1 and 13 mRNA expression in normal articular human chondrocytes. Rheumatol Int 26, 900–903 (2006). https://doi.org/10.1007/s00296-006-0114-7
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DOI: https://doi.org/10.1007/s00296-006-0114-7