Soluble CD14 Induces Pro-inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synovial Cells via Toll-Like Receptor 4

• Ichise, Yoshihide

• 三枝, 淳

• Tanaka-Natsui, Shino

• Naka, Ikuko

• 林, 申也

• 黒田, 良祐

• 森信, 暁雄

抄録

Objectives: Synovial fluids of rheumatoid arthritis (RA) patients commonly contain high concentrations of soluble CD14 (sCD14). To investigate its potential role in RA pathogenesis, we tested whether sCD14 binding transmits a signal to fibroblast-like synoviocytes from RA patients (RA-FLS). Methods: The induction of pro-inflammatory cytokines, chemokines, and mediators by sCD14 stimulation of RA-FLS was quantified by real-time PCR and ELISA. Cell proliferation was assessed by the BrdU assay. LPS-RS, a Toll-like receptor 4 (TLR-4) antagonist, was used to block TLR-4 signaling. Results: Soluble CD14 induced the expression of IL-6 mRNA and secretion of the protein. The expression of other pro-inflammatory cytokines and mediators, such as TNF-α, IL-8, intercellular adhesion molecule-1 (ICAM-1), MMP-3, and RANK ligand (RANKL), was also induced by sCD14. In addition, sCD14 stimulation promoted RA-FLS proliferation. LPS-RS abolished IL-6, IL-8, and ICAM-1 mRNA induction by sCD14 in RA-FLS. On the other hand, TNF-α and IL-17A increased TLR-4 expression by RA-FLS and amplified their sCD14-induced IL-6 expression. Conclusions: Soluble CD14 transmits inflammatory signals to RA-FLS via TLR-4. The effects of sCD14 may be augmented in inflammatory milieu. Our results suggest that sCD14 is involved in the pathogenesis of RA and may be a novel therapeutic target.

収録刊行物

• Cells

  Cells 9 (7), 1689-1689, 2020-07

  MDPI

キーワード

• fibroblast-like synoviocytes
• rheumatoid arthritis
• Soluble CD14
• TLR-4
• IL-6
• TNF-α
• IL-17A
• endogenous activator

詳細情報

• CRID: 1050294045368965504
• NII論文ID: 120006878581
• ISSN: 20734409
• HANDLE: 20.500.14094/90007375
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles