PMID- 16368150
OWN - NLM
STAT- MEDLINE
DCOM- 20080314
LR  - 20131121
IS  - 0165-2478 (Print)
IS  - 0165-2478 (Linking)
VI  - 103
IP  - 2
DP  - 2006 Mar 15
TI  - Interleukin-18 induces the production of vascular endothelial growth factor 
      (VEGF) in rheumatoid arthritis synovial fibroblasts via AP-1-dependent pathways.
PG  - 159-66
AB  - Interleukin-18 (IL-18) is a novel pro-inflammatory cytokine which has been 
      implicated to play a pathogenic role in rheumatoid arthritis (RA). Vascular 
      endothelial growth factor (VEGF) plays an important role in angiogenesis in 
      rheumatoid synoviocytes. In present study, we examined the effect of IL-18 on 
      VEGF production in fibroblast-like synoviocytes (FLS) isolated from the patients 
      with RA. FLS were prepared from the synovial tissues of patients with RA and 
      osteoarthritis (OA) and cultured in the presence of IL-18. The production of VEGF 
      from FLS was measured in culture supernatants by enzyme-linked immunosorbent 
      assay (ELISA). The VEGF messenger RNA (mRNA) expression and AP-1 binding activity 
      of VEGF transcript were determined by reverse transcription-polymerase chain 
      reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA). IL-18 and VEGF 
      levels of sera and synovial fluids (SF) of RA patients (n=30) were significantly 
      higher than those of OA patients (n=20). IL-18 dose-dependently increased the 
      production of VEGF. The effect of IL-18 on VEGF production appeared to be as 
      potent as IL-1beta, whereas tumor necrosis factor (TNF)-alpha and interferon 
      (IFN)-gamma showed little effects on VEGF production. AP-1-specific inhibitor 
      Curcumin dose-dependently abrogated the effect of IL-18 on VEGF production. The 
      VEGF enhancement of IL-18 was associated with increased AP-1 binding activity to 
      the VEGF promoter site. These findings suggest IL-18 as an angiogenic factor in 
      RA and down-regulation of IL-18 activity or AP-1 signal pathway can be potential 
      therapeutic targets for RA.
FAU - Cho, Mi-La
AU  - Cho ML
AD  - Department of Medicine, The Center for Rheumatic Diseases, The Rheumatism 
      Research Center (RhRC), Catholic Research Institutes of Medical Sciences, 
      Catholic University of Korea, Seoul 137-701, Republic of Korea. 
      iammila@catholic.ac.kr
FAU - Jung, Young Ok
AU  - Jung YO
FAU - Moon, Young-Mi
AU  - Moon YM
FAU - Min, So-Youn
AU  - Min SY
FAU - Yoon, Chong-Hyeon
AU  - Yoon CH
FAU - Lee, Sang-Heon
AU  - Lee SH
FAU - Park, Sung-Hwan
AU  - Park SH
FAU - Cho, Chul-Soo
AU  - Cho CS
FAU - Jue, Dae-Myung
AU  - Jue DM
FAU - Kim, Ho-Youn
AU  - Kim HY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051116
PL  - Netherlands
TA  - Immunol Lett
JT  - Immunology letters
JID - 7910006
RN  - 0 (Interleukin-18)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9007-49-2 (DNA)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Arthritis, Rheumatoid/*metabolism
MH  - Cells, Cultured
MH  - Curcumin/pharmacology
MH  - DNA/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Fibroblasts/*physiology
MH  - Humans
MH  - Interleukin-18/*physiology
MH  - Male
MH  - Middle Aged
MH  - Protein Binding
MH  - RNA, Messenger/metabolism
MH  - Synovial Fluid/metabolism
MH  - Synovial Membrane/*metabolism
MH  - Transcription Factor AP-1/antagonists & inhibitors/*physiology
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A/*biosynthesis/genetics
EDAT- 2005/12/22 09:00
MHDA- 2008/03/15 09:00
CRDT- 2005/12/22 09:00
PHST- 2005/10/04 00:00 [received]
PHST- 2005/10/27 00:00 [revised]
PHST- 2005/10/27 00:00 [accepted]
PHST- 2005/12/22 09:00 [pubmed]
PHST- 2008/03/15 09:00 [medline]
PHST- 2005/12/22 09:00 [entrez]
AID - S0165-2478(05)00340-8 [pii]
AID - 10.1016/j.imlet.2005.10.020 [doi]
PST - ppublish
SO  - Immunol Lett. 2006 Mar 15;103(2):159-66. doi: 10.1016/j.imlet.2005.10.020. Epub 
      2005 Nov 16.