Regulation of aggrecanase-1 and aggrecanase-2 expressions by hypoxia and cytokines in rheumatoid fibroblast-like synoviocytes / 대한내과학회지
Korean Journal of Medicine
;
: 182-188, 2006.
Article
in Korean
| WPRIM
| ID: wpr-91910
ABSTRACT
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.CONCLUSIONS:
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Arthritis, Rheumatoid
/
RNA, Messenger
/
Cartilage
/
Up-Regulation
/
Polymerase Chain Reaction
/
Cytokines
/
Transforming Growth Factor beta
/
Interleukin-6
/
Tumor Necrosis Factor-alpha
/
Epidermal Growth Factor
Limits:
Humans
Language:
Korean
Journal:
Korean Journal of Medicine
Year:
2006
Type:
Article
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