PMID- 19056796
OWN - NLM
STAT- MEDLINE
DCOM- 20090225
LR  - 20220408
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Linking)
VI  - 48
IP  - 1
DP  - 2009 Jan
TI  - Cordycepin inhibits IL-1beta-induced MMP-1 and MMP-3 expression in rheumatoid 
      arthritis synovial fibroblasts.
PG  - 45-8
LID - 10.1093/rheumatology/ken417 [doi]
AB  - OBJECTIVE: MMP is a key enzyme in the degradation of extracellular matrices, and 
      its expression plays important roles in inflammatory diseases. Cordycepin 
      (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has been shown 
      to exhibit many pharmacological activities, such as anti-cancer, 
      anti-inflammatory and anti-infection activities. In this study, we aimed at the 
      inhibitory effect of cordycepin on IL-1beta-induced MMP-1 and MMP-3 expression as 
      well as the molecular basis using RA synovial fibroblasts (RASFs). METHODS: RASFs 
      were isolated from synovial tissue obtained from 12 patients with RA and cultured 
      in monolayer. Expression of MMP-1 and MMP-3 was evaluated using western blotting 
      and real-time PCR. Chemokines were analysed by ELISA. The phosphorylation of 
      mitogen-activated protein kinase was measured by western blotting. 
      Electrophoretic mobility shift assay was performed to evaluate binding activities 
      of DNA to nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). 
      RESULTS: Cordycepin inhibited IL-1beta-induced MMP-1 and MMP-3 expressions in 
      RASFs in a dose-dependent manner. Among various chemokines [such as monocyte 
      chemoattractant protein-1 (MCP-1), GRO-alpha, regulated upon activation, normal 
      T-cell expressed and presumably secreted (RANTES) and epithelial neutrophil 
      activating peptide 78 (ENA-78)], cordycepin specifically blocked IL-1beta-induced 
      ENA-78 production in RASF. Moreover, cordycepin significantly inhibited 
      IL-1beta-induced p38/JNK and AP-1 activation, but not extracellular 
      signal-regulated kinase (ERK) and NF-kappaB activation. CONCLUSIONS: Cordycepin 
      is a potent inhibitor of IL-1beta-induced chemokine production and MMP expression 
      and strongly blocks the p38/JNK/AP-1 signalling pathway in RASFs.
FAU - Noh, E-M
AU  - Noh EM
AD  - Department of Biochemistry, Institute for Medical Science, Chonbuk National 
      University Medical School, Jeonju, South Korea.
FAU - Kim, J-S
AU  - Kim JS
FAU - Hur, H
AU  - Hur H
FAU - Park, B-H
AU  - Park BH
FAU - Song, E-K
AU  - Song EK
FAU - Han, M-K
AU  - Han MK
FAU - Kwon, K-B
AU  - Kwon KB
FAU - Yoo, W-H
AU  - Yoo WH
FAU - Shim, I-K
AU  - Shim IK
FAU - Lee, S J
AU  - Lee SJ
FAU - Youn, H J
AU  - Youn HJ
FAU - Lee, Y-R
AU  - Lee YR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Chemokines)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Deoxyadenosines)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor AP-1)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.7 (MMP1 protein, human)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
RN  - GZ8VF4M2J8 (cordycepin)
SB  - IM
MH  - Antirheumatic Agents/*pharmacology
MH  - Arthritis, Rheumatoid/*enzymology/immunology/pathology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokines/biosynthesis
MH  - DNA-Binding Proteins/metabolism
MH  - Deoxyadenosines/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical/methods
MH  - Fibroblasts/drug effects/enzymology/pathology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Humans
MH  - Interleukin-1beta/*antagonists & inhibitors/pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Matrix Metalloproteinase 1/*biosynthesis/genetics
MH  - Matrix Metalloproteinase 3/*biosynthesis/genetics
MH  - NF-kappa B/metabolism
MH  - Synovial Membrane/drug effects/enzymology/pathology
MH  - Transcription Factor AP-1/metabolism
MH  - Up-Regulation/drug effects
EDAT- 2008/12/06 09:00
MHDA- 2009/02/26 09:00
CRDT- 2008/12/06 09:00
PHST- 2008/12/06 09:00 [pubmed]
PHST- 2009/02/26 09:00 [medline]
PHST- 2008/12/06 09:00 [entrez]
AID - ken417 [pii]
AID - 10.1093/rheumatology/ken417 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2009 Jan;48(1):45-8. doi: 10.1093/rheumatology/ken417.