The production of CXCR3-agonistic chemokines by synovial fibroblasts from patients with rheumatoid arthritis

Akiko Ueno, Masahiro Yamamura, Mitsuhiro Iwahashi, Akira Okamoto, Tetsushi Aita, Norio Ogawa, Hirofumi Makino

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 languageEnglish
Pages (from-to)361-367
Number of pages7
JournalRheumatology International
Volume25
Issue number5
DOIs
Publication statusPublished - Jul 1 2005

Fingerprint

Chemokines
Rheumatoid Arthritis
Fibroblasts
Interferon-gamma
Ligands
Interleukin-1beta
Osteoarthritis
Chemokine CXCL11
Chemokine CXCL9
Proteins
Chemokine CXCL10
Messenger RNA
Th1 Cells
Chemokine Receptors
Synovial Fluid
Tumor Necrosis Factor-alpha
Joints
Cell Line

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 journalArticle

Ueno, Akiko ; Yamamura, Masahiro ; Iwahashi, Mitsuhiro ; Okamoto, Akira ; Aita, Tetsushi ; Ogawa, Norio ; Makino, Hirofumi. / The production of CXCR3-agonistic chemokines by synovial fibroblasts from patients with rheumatoid arthritis. In: Rheumatology International. 2005 ; Vol. 25, No. 5. pp. 361-367.
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