Expression and function of the NALP3 inflammasome in rheumatoid synovium

Article Article scientifique Article Expression and function of the NALP3 inflammasome in rheumatoid synovium eng 2010 author Kolly Laeticia author Busso Nathalie author Palmer-Lourenco Gaby 0000-0001-7567-1798 45743 author Talabot-Ayer Dominique author Chobaz Véronique 751349 author So Alexander 178-185 10.1111/j.1365-2567.2009.03174.x 19824913 0019-2805 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814460/pdf/imm0129-0178.pdf 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. Aged Aged, 80 and over Apoptosis Regulatory Proteins/genetics/immunology/metabolism Arthritis, Rheumatoid/genetics/immunology/metabolism B-Lymphocytes/immunology/metabolism/pathology Carrier Proteins/genetics/immunology/metabolism Caspase 1/metabolism Cell Line Endothelial Cells/immunology/metabolism/pathology Female Fibroblasts/immunology/metabolism/pathology Humans Interleukin-1beta/secretion Male Middle Aged Myeloid Cells/immunology/metabolism/pathology Nod Signaling Adaptor Proteins/genetics/immunology/metabolism Osteoarthritis/genetics/immunology/metabolism Ribonucleoproteins/genetics/immunology/metabolism Synovial Membrane/metabolism/pathology T-Lymphocytes/immunology/metabolism/pathology Dewey 616 56 Département de médecine 221 false 1326 Biologie des cytokines de la famille de l'interleukine-1 1022 28 Inflammation articulaire 44 Immunology 129 2 bee7c55b-7379-44e1-abb2-5721053a5850 Article (Published version) Restricted file1.pdf 332921 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Expression and function of the NALP3 inflammasome in rheumatoid synovium	Immunology			2010	579	0

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