α-MSH inhibits TNF-α-induced matrix metalloproteinase-13 expression by modulating p38 kinase and nuclear factor κB signaling in human chondrosarcoma HTB-94 cells

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Title
α-MSH inhibits TNF-α-induced matrix metalloproteinase-13 expression by modulating p38 kinase and nuclear factor κB signaling in human chondrosarcoma HTB-94 cells
Author(s)
Sun Woo Yoon; J S Chun; M H Sung; J Y Kim; Haryoung Poo
Bibliographic Citation
Osteoarthritis and Cartilage, vol. 16, no. 1, pp. 115-124
Publication Year
2008
Abstract
Objective: Proinflammatory cytokine-induced expression of matrix metalloproteinases (MMPs) is a major cause of arthritic cartilage destruction. The neuropeptide, α-melanocyte-stimulating hormone (α-MSH), has been detected in the synovial fluid of arthritis patients, where it is thought to play an anti-inflammatory role. Here, we examined whether α-MSH acts via downregulation of MMP expression, and sought to elucidate the intracellular signal pathways underlying this effect. Design: Human chondrosarcoma cell line, HTB-94 (SW1353) was pretreated with or without α-MSH and then treated with tumor necrosis factor-α (TNF-α). The effect of α-MSH on TNF-α-induced MMP-13 expression and mitogen-activated protein kinases' (MAPKs) activation were determined by reverse transcriptase-polymerase chain reaction and Western blot analysis. Additionally, the intracellular signaling of α-MSH was investigated using the inhibitors of MAPK and nuclear factor κB (NF-κB) and plasmids encoding dominant negative (dn) forms of inhibitor κB kinase-α (IKKα) and inhibitor κB kinase-β (IKKβ). Results: We found that α-MSH pretreatment inhibited TNF-α-induced MMP-13 expression and p38 kinase phosphorylation in HTB-94 human chondrosarcoma cells. TNF-α-induced MMP-13 expression was not suppressed by extracellular signal-regulated kinase (ERK) inhibitors (PD98059 and U0126) or a c-jun terminal kinase (JNK) inhibitor (SP600125), but was inhibited by inhibitors of p38 kinase (SB203580) and NF-κB (SN-50 peptide) and dnIKKα and dnIKKβ. Conclusions: Our results suggest that α-MSH regulates TNF-α-induced MMP-13 expression by decreasing p38 kinase phosphorylation and subsequent NF-κB activation in human chondrocytes and may be an effective inhibitor of MMP-13-mediated collagen degradation, providing new potential opportunities for the development of anti-arthritis therapeutics.
Keyword
α-MSHHTB-94 cellIKKMMP-13NF-κBp38 MAP kinaseTNF-α
ISSN
1063-4584
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.joca.2007.05.026
Type
Article
Appears in Collections:
Division of Biomaterials Research > Bionanotechnology Research Center > 1. Journal Articles
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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