Expression of toll-like receptor 2 on CD16+ blood monocytes and synovial tissue macrophages in rheumatoid arthritis
| العنوان: | Expression of toll-like receptor 2 on CD16+ blood monocytes and synovial tissue macrophages in rheumatoid arthritis |
|---|---|
| المؤلفون: | T. Aita, Sachiko Akashi, Akira Okamoto, Hirofumi Makino, Mitsuhiro Iwahashi, Masahiro Yamamura, A. Ueno, Kensuke Miyake, Norio Ogawa, Paul J. Godowski |
| المصدر: | Arthritis & Rheumatism. 50:1457-1467 |
| بيانات النشر: | Wiley, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Adult, Lipopolysaccharides, Male, medicine.medical_treatment, CD14, Immunology, Lipopolysaccharide Receptors, Receptors, Cell Surface, chemical and pharmacologic phenomena, CD16, Ligands, Antibodies, Monocytes, Proinflammatory cytokine, Arthritis, Rheumatoid, Transforming Growth Factor beta1, Rheumatology, Transforming Growth Factor beta, medicine, Humans, Immunology and Allergy, Macrophage, Pharmacology (medical), Cells, Cultured, Membrane Glycoproteins, Tumor Necrosis Factor-alpha, Chemistry, Macrophage Colony-Stimulating Factor, Macrophages, Monocyte, Receptors, IgG, Synovial Membrane, Toll-Like Receptors, NF-kappa B, Chaperonin 60, Middle Aged, Flow Cytometry, Toll-Like Receptor 2, Interleukin-10, Teichoic Acids, Toll-Like Receptor 4, Cytokine, medicine.anatomical_structure, Cytokines, Interleukin 19, Female, Synovial membrane |
| الوصف: | Objective CD16 (IgG Fcgamma receptor type IIIA [FcgammaRIIIA])-expressing CD14+ monocytes express high levels of Toll-like receptor 2 (TLR-2) and are able to efficiently produce proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha). To understand the role of CD16 and TLR-2 in monocyte and macrophage activation in rheumatoid arthritis (RA), we investigated the expression of TLR-2 on CD16+ blood monocytes and synovial tissue macrophages and the effect of CD16 and TLR-2 activation on cytokine production. Methods The expression of CD14, CD16, TLR-2, and TLR-4 on blood monocytes was measured by flow cytometric analysis. CD16 and TLR-2 expression in RA synovial tissue was detected by 2-color immunofluorescence labeling. CD16+ mature monocytes were prepared by incubating blood monocytes in plastic plates for 24 hours. These adhered monocytes were stimulated with lipoteichoic acid (LTA), anti-FcgammaRIII antibody, and Hsp60 for 5 hours, and culture supernatants were measured for various cytokines by immunoassay. The activation of NF-kappaB was detected by electrophoretic mobility shift assay. Results The frequency of CD16+ cells in all blood monocytes was significantly increased in patients with RA compared with healthy controls. TLR-2 was expressed at higher levels on CD16+ monocytes than on CD16- monocytes, while TLR-4 was expressed similarly on both monocytes. In RA synovial tissue, CD16+/TLR-2+ cells were distributed mainly in the lining layer. TLR-2 expression on monocytes was enhanced by macrophage colony-stimulating factor (M-CSF) and interleukin-10 (IL-10), but was reduced by transforming growth factor beta1, while CD16 expression was inducible by these cytokines. Adhered monocytes ( approximately 50% CD16+) produced TNFalpha, IL-1beta, IL-6, IL-8, IL-12 p40, IL-1 receptor antagonist, and IL-10 after LTA stimulation. This cytokine response was inhibited significantly by anti-TLR-2 antibody and partly by anti-TLR-4 antibody. Anti-FcgammaRIII antibody stimulation markedly enhanced the LTA-induced TNFalpha response. Hsp60 could stimulate TNFalpha production by adhered monocytes, which was inhibited similarly by anti-TLR-2 antibody and anti-TLR-4 antibody. NF-kappaB activation in adhered monocytes was induced by LTA, but this NF-kappaB activity was not augmented by anti-FcgammaRIII antibody stimulation. Conclusion These results suggest that CD16+ monocytes and synovial tissue macrophages with high TLR-2 expression may be induced by M-CSF and IL-10, and their production of TNFalpha could be simulated by endogenous TLR ligands such as Hsp60 and FcgammaRIIIA ligation by small immune complexes in RA joints. |
| تدمد: | 1529-0131 0004-3591 |
| DOI: | 10.1002/art.20219 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4d3c380e4b71d08ae5765eeb87683ac4 https://doi.org/10.1002/art.20219 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4d3c380e4b71d08ae5765eeb87683ac4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15290131 00043591 |
|---|---|
| DOI: | 10.1002/art.20219 |