PMID- 14652683
OWN - NLM
STAT- MEDLINE
DCOM- 20040702
LR  - 20220227
IS  - 1023-3830 (Print)
IS  - 1023-3830 (Linking)
VI  - 52
IP  - 11
DP  - 2003 Nov
TI  - Effect of hypoxia on monocyte chemotactic protein-1 (MCP-1) gene expression 
      induced by Interleukin-1beta in human synovial fibroblasts.
PG  - 480-6
AB  - OBJECTIVE: Rheumatoid arthritis (RA) synovial membrane is characterized by 
      leucocyte infiltration and secretion of chemotactic and proinflammatory factors. 
      Since hypoxia is an important pathogenic factor in inflamed synovium, we examined 
      the effects of hypoxia on monocyte chemotactic protein-1 (MCP-1) expression in 
      human rheumatoid arthritis synovial fibroblasts (RASF) under IL-1beta-stimulated 
      and -unstimulated conditions. METHODS: Synovial fibroblasts were isolated from 
      RA, osteoarthritis (OA) and healthy knee joints and subjected to hypoxia or/and 
      IL-1beta treatment. MCP-1 expression and protein secretion were measured by 
      real-time PCR and ELISA, respectively. RESULTS: Hypoxia reduces MCP-1 expression 
      and protein secretion in RASF. The same response to hypoxia was found in OA and 
      healthy SF cultures. Treatment with actinomycin D showed that hypoxic 
      down-regulation of MCP-1 expression was due to a decrease in transcription, since 
      the half-life of MCP-1 mRNA was unchanged. A cycloheximide study demonstrated 
      that de novo protein synthesis was not required for the hypoxic effect. The 
      decrease in MCP-1 expression by hypoxia was mimicked by cobalt chloride in 
      unstimulated RASF with no effect on IL-1beta-activated MCP-1, suggesting 
      differences in the signaling mechanisms. The analysis of IkappaB degradation and 
      NF-kappaB translocation revealed that hypoxia did not affect IL-1beta activation 
      of NF-kappaB. CONCLUSION: Hypoxia regulates MCP-1 expression under both basal and 
      cytokine-stimulated conditions, suggesting that reduced oxygen supply is an 
      important factor that mediates chemotaxis of monocytes to the area of 
      inflammation.
FAU - Safronova, O
AU  - Safronova O
AD  - Department of Cellular Physiological Chemistry, 1-5-45, Yushima, Bunkyo-ku, 
      113-8549, Tokyo, Japan.
FAU - Nakahama, K
AU  - Nakahama K
FAU - Onodera, M
AU  - Onodera M
FAU - Muneta, T
AU  - Muneta T
FAU - Morita, I
AU  - Morita I
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - 3G0H8C9362 (Cobalt)
RN  - 98600C0908 (Cycloheximide)
RN  - EVS87XF13W (cobaltous chloride)
SB  - IM
EIN - Inflamm Res. 2004 Apr;53(4):170
MH  - Arthritis, Rheumatoid/metabolism
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis
MH  - Cobalt/metabolism/pharmacology
MH  - Cycloheximide/pharmacology
MH  - Dactinomycin/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fibroblasts/*metabolism
MH  - *Gene Expression Regulation
MH  - Humans
MH  - *Hypoxia
MH  - Inflammation
MH  - Interleukin-1/metabolism/*physiology
MH  - Knee/pathology
MH  - Osteoarthritis/metabolism
MH  - Polymerase Chain Reaction
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Synovial Membrane/*metabolism
MH  - Time Factors
EDAT- 2003/12/04 05:00
MHDA- 2004/07/03 05:00
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/07/03 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
AID - 10.1007/s00011-003-1205-5 [doi]
PST - ppublish
SO  - Inflamm Res. 2003 Nov;52(11):480-6. doi: 10.1007/s00011-003-1205-5.