Abstract
The inflamed synovial tissue of rheumatoid arthritis (RA) is characterized by an infiltration with Th1 cells that predominantly express the chemokine receptors CXCR3 and CCR5. In this study, we investigated the production of the CXCR3-agonistic chemokines CXCL9, CXCL10, and CXCL11 by synovial tissue cells and synovial fibroblast-cell lines (fourth or fifth passage) from RA patients. Concentrations of all CXCR3 ligands in synovial fluids were markedly higher in RA patients than in osteoarthritis (OA) patients. Synovial tissue cells from RA patients more strongly expressed mRNAs for CXCR3 ligands and spontaneously secreted larger amounts of these chemokine proteins than the cells from OA patients. The mRNA expression of all CXCR3 ligands was induced in synovial fibroblasts from RA patients after stimulation with interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), or interleukin-1 beta (IL-1β). However, synovial fibroblasts significantly secreted CXCL9 and CXCL10 proteins, but not CXCL11 protein, after IFN-γ stimulation and secreted only CXCL10 protein after TNF-α or IL-1β stimulation. When stimulated with a combination of IFN-γ and TNF-α, these cells were able to secrete large amounts of all three chemokines. These results indicate that synovial fibroblasts may be involved in perpetuating the Th1 immune response by producing the Th1-associated CXCR3 ligands, and the synergistic effect of IFN-γ and TNF-α may be important for their chemokine production in RA joints.
| Original language | English |
|---|---|
| Pages (from-to) | 361-367 |
| Number of pages | 7 |
| Journal | Rheumatology International |
| Volume | 25 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Jul 1 2005 |
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Keywords
- CXCL10
- CXCL11
- CXCL9
- Rheumatoid arthritis
- Synovial fibroblasts
ASJC Scopus subject areas
- Rheumatology
- Immunology and Allergy
- Immunology
Cite this
The production of CXCR3-agonistic chemokines by synovial fibroblasts from patients with rheumatoid arthritis. / Ueno, Akiko; Yamamura, Masahiro; Iwahashi, Mitsuhiro; Okamoto, Akira; Aita, Tetsushi; Ogawa, Norio; Makino, Hirofumi.
In: Rheumatology International, Vol. 25, No. 5, 01.07.2005, p. 361-367.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The production of CXCR3-agonistic chemokines by synovial fibroblasts from patients with rheumatoid arthritis
AU - Ueno, Akiko
AU - Yamamura, Masahiro
AU - Iwahashi, Mitsuhiro
AU - Okamoto, Akira
AU - Aita, Tetsushi
AU - Ogawa, Norio
AU - Makino, Hirofumi
PY - 2005/7/1
Y1 - 2005/7/1
N2 - The inflamed synovial tissue of rheumatoid arthritis (RA) is characterized by an infiltration with Th1 cells that predominantly express the chemokine receptors CXCR3 and CCR5. In this study, we investigated the production of the CXCR3-agonistic chemokines CXCL9, CXCL10, and CXCL11 by synovial tissue cells and synovial fibroblast-cell lines (fourth or fifth passage) from RA patients. Concentrations of all CXCR3 ligands in synovial fluids were markedly higher in RA patients than in osteoarthritis (OA) patients. Synovial tissue cells from RA patients more strongly expressed mRNAs for CXCR3 ligands and spontaneously secreted larger amounts of these chemokine proteins than the cells from OA patients. The mRNA expression of all CXCR3 ligands was induced in synovial fibroblasts from RA patients after stimulation with interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), or interleukin-1 beta (IL-1β). However, synovial fibroblasts significantly secreted CXCL9 and CXCL10 proteins, but not CXCL11 protein, after IFN-γ stimulation and secreted only CXCL10 protein after TNF-α or IL-1β stimulation. When stimulated with a combination of IFN-γ and TNF-α, these cells were able to secrete large amounts of all three chemokines. These results indicate that synovial fibroblasts may be involved in perpetuating the Th1 immune response by producing the Th1-associated CXCR3 ligands, and the synergistic effect of IFN-γ and TNF-α may be important for their chemokine production in RA joints.
AB - The inflamed synovial tissue of rheumatoid arthritis (RA) is characterized by an infiltration with Th1 cells that predominantly express the chemokine receptors CXCR3 and CCR5. In this study, we investigated the production of the CXCR3-agonistic chemokines CXCL9, CXCL10, and CXCL11 by synovial tissue cells and synovial fibroblast-cell lines (fourth or fifth passage) from RA patients. Concentrations of all CXCR3 ligands in synovial fluids were markedly higher in RA patients than in osteoarthritis (OA) patients. Synovial tissue cells from RA patients more strongly expressed mRNAs for CXCR3 ligands and spontaneously secreted larger amounts of these chemokine proteins than the cells from OA patients. The mRNA expression of all CXCR3 ligands was induced in synovial fibroblasts from RA patients after stimulation with interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), or interleukin-1 beta (IL-1β). However, synovial fibroblasts significantly secreted CXCL9 and CXCL10 proteins, but not CXCL11 protein, after IFN-γ stimulation and secreted only CXCL10 protein after TNF-α or IL-1β stimulation. When stimulated with a combination of IFN-γ and TNF-α, these cells were able to secrete large amounts of all three chemokines. These results indicate that synovial fibroblasts may be involved in perpetuating the Th1 immune response by producing the Th1-associated CXCR3 ligands, and the synergistic effect of IFN-γ and TNF-α may be important for their chemokine production in RA joints.
KW - CXCL10
KW - CXCL11
KW - CXCL9
KW - Rheumatoid arthritis
KW - Synovial fibroblasts
UR - http://www.scopus.com/inward/record.url?scp=21544443147&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=21544443147&partnerID=8YFLogxK
U2 - 10.1007/s00296-004-0449-x
DO - 10.1007/s00296-004-0449-x
M3 - Article
C2 - 15004722
AN - SCOPUS:21544443147
VL - 25
SP - 361
EP - 367
JO - Rheumatology International
JF - Rheumatology International
SN - 0172-8172
IS - 5
ER -