Soluble CD14 Induces Pro-inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synovial Cells via Toll-Like Receptor 4
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:...
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MDPI AG
2020-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/7/1689 |
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| author | Yoshihide Ichise Jun Saegusa Shino Tanaka-Natsui Ikuko Naka Shinya Hayashi Ryosuke Kuroda Akio Morinobu |
| author_facet | Yoshihide Ichise Jun Saegusa Shino Tanaka-Natsui Ikuko Naka Shinya Hayashi Ryosuke Kuroda Akio Morinobu |
| author_sort | Yoshihide Ichise |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T18:29:55Z |
| format | Article |
| id | doaj.art-b65e34af03b14d0b92cb3663c98b2f91 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:29:55Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b65e34af03b14d0b92cb3663c98b2f912023-11-20T06:43:30ZengMDPI AGCells2073-44092020-07-0197168910.3390/cells9071689Soluble CD14 Induces Pro-inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synovial Cells via Toll-Like Receptor 4Yoshihide Ichise0Jun Saegusa1Shino Tanaka-Natsui2Ikuko Naka3Shinya Hayashi4Ryosuke Kuroda5Akio Morinobu6Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Orthopedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Orthopedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanObjectives: 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.https://www.mdpi.com/2073-4409/9/7/1689fibroblast-like synoviocytesrheumatoid arthritisSoluble CD14TLR-4IL-6TNF-α |
| spellingShingle | Yoshihide Ichise Jun Saegusa Shino Tanaka-Natsui Ikuko Naka Shinya Hayashi Ryosuke Kuroda Akio Morinobu Soluble CD14 Induces Pro-inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synovial Cells via Toll-Like Receptor 4 Cells fibroblast-like synoviocytes rheumatoid arthritis Soluble CD14 TLR-4 IL-6 TNF-α |
| title | Soluble CD14 Induces Pro-inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synovial Cells via Toll-Like Receptor 4 |
| title_full | Soluble CD14 Induces Pro-inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synovial Cells via Toll-Like Receptor 4 |
| title_fullStr | Soluble CD14 Induces Pro-inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synovial Cells via Toll-Like Receptor 4 |
| title_full_unstemmed | Soluble CD14 Induces Pro-inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synovial Cells via Toll-Like Receptor 4 |
| title_short | Soluble CD14 Induces Pro-inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synovial Cells via Toll-Like Receptor 4 |
| title_sort | soluble cd14 induces pro inflammatory cytokines in rheumatoid arthritis fibroblast like synovial cells via toll like receptor 4 |
| topic | fibroblast-like synoviocytes rheumatoid arthritis Soluble CD14 TLR-4 IL-6 TNF-α |
| url | https://www.mdpi.com/2073-4409/9/7/1689 |
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