ArticleArthritis research & therapy2014
Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction.
Article in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 103 citations in OpenAlex.
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- Pyroptosis by NLRP3/caspase-1/gasdermin-D pathway in synovial tissues of rheumatoid arthritis patients.Journal of cellular and molecular medicine · 2023Article
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- NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs.International journal of biological sciences · 2023Article
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- Trivalent chromium supplementation ameliorates adjuvant induced rheumatoid arthritis through up-regulation of FOXP3 and decrease in synovial Cathepsin G expression.Inflammopharmacology · 2022Article
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- Exosomes derived from heat shock preconditioned bone marrow mesenchymal stem cells alleviate cisplatin-induced ototoxicity in mice.Journal of biological engineering · 2022Article
- IL-10 Induced by mTNF Crosslinking-Mediated Reverse Signaling in a Whole Blood Assay Is Predictive of Response to TNFi Therapy in Rheumatoid Arthritis.Journal of personalized medicine · 2022Article
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Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
Abstract
introductionActivation of the inflammasome has been implicated in the pathology of various autoinflammatory and autoimmune diseases. While the NLRP3 inflammasome has been linked to arthritis progression, little is known about its synovial regulation or contribution to joint histopathology. Regulators of inflammation activation, such as interleukin (IL)-10, may have the potential to limit the inflammasome-driven arthritic disease course and associated structural damage. Hence, we used IL-10-deficient (IL-10KO) mice to assess NLRP3 inflammasome-driven arthritic pathology.
methodsAntigen-induced arthritis (AIA) was established in IL-10KO mice and wild-type controls. Using histological and radiographic approaches together with quantitative real-time PCR of synovial mRNA studies, we explored the regulation of inflammasome components. These were combined with selective blocking agents and ex vivo investigative studies in osteoclast differentiation assays.
resultsIn AIA, IL-10KO mice display severe disease with increased histological and radiographic joint scores. Here, focal bone erosions were associated with increased tartrate-resistant acid phosphatase (TRAP)-positive cells and a localized expression of IL-1β. When compared to controls, IL-10KO synovium showed increased expression of Il1b, Il33 and NLRP3 inflammasome components. Synovial Nlrp3 and Casp1 expression further correlated with Acp5 (encoding TRAP), while neutralization of IL-10 receptor signaling in control mice caused increased expression of Nlrp3 and Casp1. In ex vivo osteoclast differentiation assays, addition of exogenous IL-10 or selective blockade of the NLRP3 inflammasome inhibited osteoclastogenesis.
conclusionsThese data provide a link between IL-10, synovial regulation of the NLRP3 inflammasome and the degree of bone erosions observed in inflammatory arthritis.
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