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Expression and function of the NALP3 inflammasome in rheumatoid synovium

Kolly, Laeticia
Busso, Nathalie
Talabot-Ayer, Dominique
So, Alexander
Published in Immunology. 2010, vol. 129, no. 2, p. 178-185
Abstract The NACHT, LRR and PYD domains containing protein (NALP3) inflammasome is a key regulator of interleukin-1 beta (IL-1 beta) secretion. As there is strong evidence for a pro-inflammatory role of IL-1 beta in rheumatoid arthritis (RA) and in murine models of arthritis, we explored the expression of the different components of the NALP3 inflammasome as well as other nucleotide oligomerization domain (NOD)-like receptors (NLRs) in synovium obtained from patients with RA. The expression of NLRs was also studied in fibroblast lines derived from joint tissue. By immunohistology, NALP3 and apoptosis-associated speck-like protein containing a CARD domain (ASC) were expressed in myeloid and endothelial cells and B cells. T cells expressed ASC but lacked NALP3. In synovial fibroblast lines, NALP3 expression was not detected at the RNA and protein levels and stimulation with known NALP3 agonists failed to induce IL-1 beta secretion. Interestingly, we were unable to distinguish RA from osteoarthritis synovial samples on the basis of their basal level of RNA expression of known NLR proteins, though RA samples contained higher levels of caspase-1 assayed by enzyme-linked immunosorbent assay. These results indicate that myeloid and endothelial cells are the principal sources of inflammasome-mediated IL-1 beta production in the synovium, and that synovial fibroblasts are unable to activate caspase-1 because they lack NALP3. The NALP3 inflammasome activity does not account for the difference in level of inflammation between RA and osteoarthritis.
Keywords AgedAged, 80 and overApoptosis Regulatory Proteins/genetics/immunology/metabolismArthritis, Rheumatoid/genetics/*immunology/metabolismB-Lymphocytes/immunology/metabolism/pathologyCarrier Proteins/genetics/immunology/*metabolismCaspase 1/metabolismCell LineEndothelial Cells/immunology/metabolism/pathologyFemaleFibroblasts/immunology/metabolism/pathologyHumansInterleukin-1beta/secretionMaleMiddle AgedMyeloid Cells/immunology/metabolism/pathologyNod Signaling Adaptor Proteins/genetics/immunology/*metabolismOsteoarthritis/genetics/*immunology/metabolismRibonucleoproteins/genetics/immunology/metabolismSynovial Membrane/*metabolism/pathologyT-Lymphocytes/immunology/metabolism/pathology
PMID: 19824913
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Research groups Mécanisme de l'inflammation articulaire (44)
Biologie des cytokines de la famille de l'interleukine-1 (1022)
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KOLLY, Laeticia et al. Expression and function of the NALP3 inflammasome in rheumatoid synovium. In: Immunology, 2010, vol. 129, n° 2, p. 178-185. doi: 10.1111/j.1365-2567.2009.03174.x https://archive-ouverte.unige.ch/unige:21049

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Deposited on : 2012-05-23

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