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KMID : 0882420060710020182
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Korean Journal of Medicine
2006 Volume.71 No. 2 p.182 ~ p.188
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Regulation of aggrecanase-1 and aggrecanase-2 expressions by hypoxia and cytokines in rheumatoid fibroblast-like synoviocytes
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Kim Hyung-Jin
Bae Eun-Kyung
Kim Jin-Hee
Chai Ji-Young
Jeon Chan-Hong
Cha Hoon-Suk
Ahn Kwang-Sung
Koh Eun-Mi
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Abstract
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Background: While aggrecanases (aggrecanase-1 and aggrecanase-2) are substantially responsible for cartilage aggrecan breakdown in rheumatoid arthritis (RA), not much information is available on the regulation or expression of the two key aggrecanases in rheumatoid fibroblast-like synoviocytes (FLS). The aim of this study is to determine the effect of hypoxia and several cytokines on the expression of the aggrecanases in rheumatoid FLS.
Methods: FLS obtained from RA patients were cultured under hypoxic condition for 24 hours. Quantitative polymerase chain reaction assays for mRNA expression of aggrecanase-1 and aggrecanase-2 were performed on FLS cultured under hypoxia. Additionally, to see the effect of various cytokines, same experiments were conducted after treating FLS with IL-1beta, IL-6, EGF, TGF-beta and TNF-alpha, compared with control.
Results: Hypoxia significantly increased both aggrecanase-1 and -2 mRNA expression in rheumatoid FLS compared with normoxia. IL-1beta, IL-6, EGF, TGF-beta and TNF-alpha upregulated the mRNA expression of aggrecanase-1. Both EGF and TGF-beta upregulated the mRNA expression of aggrecanase-2, but TNF-alpha significantly downregulated the mRNA expression of aggrecanase-2.
Conclusion: These results showed upregulation of aggrecanase-1 and -2 by hypoxia and differential regulation of aggrecanase-1 and -2 by various cytokines in rheumatoid FLS. It suggests that hypoxia and cytokines enhance the aggrecanase activity of RA FLS and contribute to joint destruction.
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KEYWORD
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Hypoxia, Aggrecanase, Rheumatoid arthritis
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