PMID- 17393416
OWN - NLM
STAT- MEDLINE
DCOM- 20070510
LR  - 20220316
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 56
IP  - 4
DP  - 2007 Apr
TI  - Up-regulation of stromal cell-derived factor 1 (CXCL12) production in rheumatoid 
      synovial fibroblasts through interactions with T lymphocytes: role of 
      interleukin-17 and CD40L-CD40 interaction.
PG  - 1076-86
AB  - OBJECTIVE: Stromal cell-derived factor 1 (SDF-1) is a potent chemoattractant for 
      memory T cells in inflamed rheumatoid arthritis (RA) synovium. This study was 
      undertaken to investigate the effect of interleukin-17 (IL-17) and CD40-CD40L 
      interaction on SDF-1 production in RA fibroblast-like synoviocytes (FLS). 
      METHODS: Synovial fluid (SF) and serum levels of SDF-1 in RA patients were 
      measured by enzyme-linked immunosorbent assay (ELISA). The SDF-1 produced by 
      cultured RA FLS was evaluated by real-time polymerase chain reaction and ELISA 
      after FLS were treated with IL-17 and inhibitors of intracellular signal 
      molecules. The SDF-1 level was also determined after FLS were cocultured with T 
      cells in the presence and absence of IL-17. RESULTS: Concentrations of SDF-1 in 
      the sera and SF were higher in RA patients than in osteoarthritis patients, 
      although the increase in the serum levels did not reach statistical significance. 
      The production of SDF-1 in RA FLS was enhanced by IL-17 stimulation. This effect 
      of IL-17 was blocked by inhibitors of phosphatidylinositol 3-kinase (PI 
      3-kinase), NF-kappaB, and activator protein 1 (AP-1). When FLS were cocultured 
      with T cells, SDF-1 production was up-regulated, especially in the presence of 
      IL-17, but FLS were inhibited by neutralizing anti-IL-17 and anti-CD40L 
      antibodies. Addition of RA SF to cultured RA FLS significantly up-regulated SDF-1 
      messenger RNA expression, which was hampered by pretreatment with anti-IL-17 
      antibody. CONCLUSION: SDF-1 is overproduced in RA FLS, and IL-17 could 
      up-regulate the expression of SDF-1 in RA FLS via pathways mediated by PI 
      3-kinase, NF-kappaB, and AP-1. Our findings suggest that inhibition of the 
      interaction between IL-17 from T cells and SDF-1 in FLS may provide a new 
      therapeutic approach in RA.
FAU - Kim, Kyoung-Woon
AU  - Kim KW
AD  - Catholic University of Korea, and Department of Internal Medicine, Konkuk 
      University Hospital, Seoul, Korea.
FAU - Cho, Mi-La
AU  - Cho ML
FAU - Kim, Hae-Rim
AU  - Kim HR
FAU - Ju, Ji-Hyeon
AU  - Ju JH
FAU - Park, Mi-Kyung
AU  - Park MK
FAU - Oh, Hye-Jwa
AU  - Oh HJ
FAU - Kim, Joon-Seok
AU  - Kim JS
FAU - Park, Sung-Hwan
AU  - Park SH
FAU - Lee, Sang-Heon
AU  - Lee SH
FAU - Kim, Ho-Youn
AU  - Kim HY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies, Blocking)
RN  - 0 (CD40 Antigens)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Interleukin-17)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Blocking/pharmacology
MH  - Arthritis, Rheumatoid/genetics/*metabolism/pathology
MH  - CD4-Positive T-Lymphocytes/drug effects/*metabolism/pathology
MH  - CD40 Antigens/metabolism
MH  - CD40 Ligand/metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokine CXCL12
MH  - Chemokines, CXC/genetics/*metabolism
MH  - Coculture Techniques
MH  - Fibroblasts/metabolism/pathology
MH  - Humans
MH  - Interleukin-17/immunology/metabolism/pharmacology
MH  - Middle Aged
MH  - Stromal Cells/*metabolism
MH  - Synovial Fluid/cytology/*metabolism
MH  - Up-Regulation
EDAT- 2007/03/30 09:00
MHDA- 2007/05/11 09:00
CRDT- 2007/03/30 09:00
PHST- 2007/03/30 09:00 [pubmed]
PHST- 2007/05/11 09:00 [medline]
PHST- 2007/03/30 09:00 [entrez]
AID - 10.1002/art.22439 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2007 Apr;56(4):1076-86. doi: 10.1002/art.22439.