Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction

Hdl Handle:
http://hdl.handle.net/10147/332072
Title:
Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction
Authors:
Greenhill, Claire J; Jones, Gareth W; Nowell, Mari A; Newton, Zarabeth; Harvey, Ann K; Moideen, Abdul N; Collins, Fraser L; Bloom, Anja C; Coll, Rebecca C; Robertson, Avril AB; Cooper, Matthew A; Rosas, Marcela; Taylor, Philip R; O’Neill, Luke A; Humphreys, Ian R; Williams, Anwen S; Jones, Simon A
Citation:
Greenhill CJ, Jones GW, Nowell MA et al. Arthritis Res & Ther. 2014 Aug 30;16(4):419
Issue Date:
30-Aug-2014
URI:
http://dx.doi.org/10.1186/s13075-014-0419-y; http://hdl.handle.net/10147/332072
Abstract:
Abstract Introduction Activation 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. Methods Antigen-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. Results In 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. Conclusions These data provide a link between IL-10, synovial regulation of the NLRP3 inflammasome and the degree of bone erosions observed in inflammatory arthritis.
Item Type:
Article
Language:
en
Keywords:
ARTHRITIS

Full metadata record

DC FieldValue Language
dc.contributor.authorGreenhill, Claire Jen_GB
dc.contributor.authorJones, Gareth Wen_GB
dc.contributor.authorNowell, Mari Aen_GB
dc.contributor.authorNewton, Zarabethen_GB
dc.contributor.authorHarvey, Ann Ken_GB
dc.contributor.authorMoideen, Abdul Nen_GB
dc.contributor.authorCollins, Fraser Len_GB
dc.contributor.authorBloom, Anja Cen_GB
dc.contributor.authorColl, Rebecca Cen_GB
dc.contributor.authorRobertson, Avril ABen_GB
dc.contributor.authorCooper, Matthew Aen_GB
dc.contributor.authorRosas, Marcelaen_GB
dc.contributor.authorTaylor, Philip Ren_GB
dc.contributor.authorO’Neill, Luke Aen_GB
dc.contributor.authorHumphreys, Ian Ren_GB
dc.contributor.authorWilliams, Anwen Sen_GB
dc.contributor.authorJones, Simon Aen_GB
dc.date.accessioned2014-10-03T14:55:43Z-
dc.date.available2014-10-03T14:55:43Z-
dc.date.issued2014-08-30-
dc.identifier.citationGreenhill CJ, Jones GW, Nowell MA et al. Arthritis Res & Ther. 2014 Aug 30;16(4):419en_GB
dc.identifier.urihttp://dx.doi.org/10.1186/s13075-014-0419-y-
dc.identifier.urihttp://hdl.handle.net/10147/332072-
dc.description.abstractAbstract Introduction Activation 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. Methods Antigen-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. Results In 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. Conclusions These data provide a link between IL-10, synovial regulation of the NLRP3 inflammasome and the degree of bone erosions observed in inflammatory arthritis.-
dc.language.isoenen
dc.subjectARTHRITISen_GB
dc.titleInterleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destructionen_GB
dc.typeArticleen
dc.language.rfc3066en-
dc.rights.holderClaire J Greenhill et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2014-10-02T15:03:05Z-
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