Amplification of the synovial inflammatory response through activation of mitogen-activated protein kinases and nuclear factor kappaB using ligation of CD40 on CD14+ synovial cells from patients with rheumatoid arthritis

Arthritis and Rheumatism
Masayoshi HarigaiNaoyuki Kamatani

Abstract

To determine the signal transduction pathways in CD14+ synovial cells from patients with rheumatoid arthritis (RA) after CD40 ligation, and to examine their role in amplifying synovial inflammation in affected joints. Expression of messenger RNA was analyzed using quantitative reverse transcription-polymerase chain reaction. Cytokines and chemokines were measured using enzyme-linked immunosorbent assay. Activation of kinases was detected using Western blotting. Nuclear translocation of NF-kappaB was examined using immunohistochemistry. CD14+ synovial cells were enriched using magnetic cell sorting. Fibroblast-like synoviocytes (FLS) were obtained by passaging primary synovial cell culture. Stimulation of CD14+ synovial cells from RA patients by recombinant soluble CD154 (rsCD154) significantly induced expression of tumor necrosis factor alpha (TNFalpha), interleukin-1alpha (IL-1alpha), and IL-1beta. CD14+ RA synovial cells stimulated with rsCD154 plus interferon-gamma (IFNgamma) induced significantly higher production of IL-6, IL-8, and monocyte chemoattractant protein 1 by FLS compared with unstimulated CD14+ synovial cells, through TNFalpha-, IL-1alpha-, and IL-1beta-mediated pathways. Stimulation with rsCD154 plus IFNgamma i...Continue Reading

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Citations

Mar 10, 2009·Rheumatology·Rachel L LakeyCatharien M U Hilkens
Mar 24, 2009·Annual Review of Immunology·Peter K Gregersen, Lina M Olsson
Feb 1, 2005·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Masayoshi Harigai
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Nov 13, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomoko SugiuraTakeshi Urano

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