Tumour necrosis factor α augments the inhibitory effects of CTLA-4-Ig on osteoclast generation from human monocytes via induction of CD80 expression.
Abatacept
/ metabolism
Aged
Arthritis, Rheumatoid
/ immunology
B7-1 Antigen
/ metabolism
Cell Differentiation
Cells, Cultured
Female
Humans
Immunomodulation
Monocytes
/ physiology
Osteoclasts
/ physiology
Osteogenesis
Synovial Fluid
/ immunology
Tumor Necrosis Factor-alpha
/ metabolism
Up-Regulation
cell differentiation
cytokine
monocyte
rheumatoid arthritis
Journal
Clinical and experimental immunology
ISSN: 1365-2249
Titre abrégé: Clin Exp Immunol
Pays: England
ID NLM: 0057202
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
accepted:
21
01
2019
pubmed:
7
2
2019
medline:
4
4
2020
entrez:
7
2
2019
Statut:
ppublish
Résumé
Cytotoxic T lymphocyte antigen-4-immunoglobulin (CTLA-4-Ig) exerts anti-rheumatic action via negative regulation of the co-stimulation process between antigen-presenting cells and T cells. CTLA-4-Ig also binds to CD80/CD86 on monocytes of osteoclast precursors. However, little is known about the effect of CTLA-4-Ig on osteoclastogenesis in rheumatoid arthritis (RA). In this study we evaluated the effects of CTLA-4-Ig on osteoclast generation from human blood monocytes (PBM) and rheumatoid synovial fluid monocytes (RSFM). Highly purified monocytes were cultured with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in the presence of CTLA-4-Ig. CTLA-4-Ig inhibited RANKL-induced osteoclast generation in PBM and RSFM, as determined by tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assay using osteo assay surface plates. In addition, CTLA-4-Ig reduced the gene and protein expressions of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) and cathepsin K during osteoclastogenesis. Furthermore, CTLA-4-Ig significantly inhibited cell proliferation during osteoclastogenesis. Interestingly, the gene expression of indoleamine 2,3-dioxygenase-1, an inducer of apoptosis, was enhanced by CTLA-4-Ig. We next examined the effect of tumour necrosis factor (TNF)-α, a major inflammatory cytokine in rheumatoid synovium, on the expression of CD80 and CD86 by flow cytometric analysis. TNF-α potently induced the surface expression of CD80, which is known to have much higher affinity to CTLA-4-Ig than CD86, and this induction was observed at mRNA levels. Interestingly, freshly prepared rheumatoid synovial monocytes also expressed CD80 as much as TNF-α-treated PBM. Furthermore, TNF-α enhanced CTLA-4-Ig-induced inhibition of osteoclastogenesis and cell proliferation. Taken together, the TNF-α-induced CD80 may augment CTLA-4-Ig-induced inhibition of osteoclastogenesis, suggesting that CTLA-4-Ig potently inhibits osteoclast differentiation and protects bone destruction in rheumatoid inflamed joints.
Identifiants
pubmed: 30724348
doi: 10.1111/cei.13271
pmc: PMC6514374
doi:
Substances chimiques
B7-1 Antigen
0
Tumor Necrosis Factor-alpha
0
Abatacept
7D0YB67S97
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
392-402Informations de copyright
© 2019 British Society for Immunology.
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