Role of mitogen-activated protein kinases and NFkappaB on IL-1beta-induced effects on collagen type II, MMP-1 and 13 mRNA expression in normal articular human chondrocytes.
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-1beta together with selective inhibitors of the ERK, JNK, p38, and NFkappaB pathways. Inhibitors of ERK and NFkappaB 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-1beta 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.
Osteoarticular and Arthritis Research Group, Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstr, 8-10, 91054 Erlangen, Germany.
Zhiyong
Z
Fan
Huiqing
H
Yang
Brigitte
B
Bau
Stephan
S
Söder
Thomas
T
Aigner
D000328:Adult; D002358:Cartilage, Articular / Q000166:cytology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D007719:Knee Joint / Q000166:cytology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D024043:Collagen Type II; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D012333:RNA, Messenger; D020928:Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1