Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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

Greenhill, Claire J., Jones, Gareth Wyn, Nowell, Mari Ann, Newton, Zarabeth, Harvey, Ann K., Moideen, Abdul Nazeer, Collins, Fraser L., Bloom, Anja C., Coll, Rebecca C., Robertson, Avril A. B., Cooper, Matthew A., Rosas, Marcela, Taylor, Philip Russel, O'Neill, Luke A., Humphreys, Ian R., Williams, Anwen Sian and Jones, Simon Arnett 2014. Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction. Arthritis Research and Therapy 16 (4) , 419. 10.1186/s13075-014-0419-y

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

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-1?. 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
Date Type: Published Online
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Publisher: BioMed Central
ISSN: 1478-6354
Funders: Arthritis Research UK
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 1 August 2014
Last Modified: 06 Feb 2019 17:30
URI: http://orca.cf.ac.uk/id/eprint/78712

Citation Data

Cited 28 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics