miR-223 targets IL-1β production and is decreased in synovial fluid monocytes from arthritis patients

Haneklaus, M., Gerlic, M., Kurowska-Stolarska, M. , Rainey, A., Pitch, D., Hammerschmidt, W., O’Neill, L. and Masters, S. (2012) miR-223 targets IL-1β production and is decreased in synovial fluid monocytes from arthritis patients. In: Australian Rheumatology Association in conjunction with Rheumatology Health Professionals 53rd Annual Scientific Meeting, Canberra, Australia, 12-15 May 2012, pp. 9-10. (doi:10.1111/j.1445-5994.2012.02761.x)

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Abstract

Aim: The aim of this study was to identify miRNA that target infl ammatory pathways during arthritis. Specifi cally we are interested in production of the key infl ammatory cytokine IL-1β, which is generated by a complex of proteins known as the infl ammasome.

Methods: Synovial fl uid monocytes were isolated from patients with rheumatoid or psoriatic arthritis and analysis of miRNA expression was performed. NLRP3, a key component of the infl ammasome, was identifi ed as a potential target of miR-223 and this was validated by several approaches.

Results: We have identifi ed the fi rst miRNA that targets an infl ammasome complex. This is miR-223, which has a single, highly conserved binding site in the NLRP3 3′UTR. miR-223 expression decreases as monocytes differentiate into macrophages, and NLRP3 protein increases during this time. However overexpression of miR-223 prevents accumulation of endogenous NLRP3 protein levels, as for monocytic Thp-1 cells differentiated into macrophages with PMA. NLRP3 function was also impacted by miR-223, with decreased IL-1β production after stimulation with nigericin or uric acid crystals, but not poly dAdT (AIM2) or salmonella (NLRC4). Consistent with this, mice lacking miR-223 are reported to have spontaneous infl ammatory disease associated with increased NLRP3 protein expression. miR-223 is known to be decreased in type 2 diabetes, Crohn’s disease, and now we show a specifi c decrease in synovial monocytes from rheumatoid and psoriatic arthritis patients. All of these diseases are associated with increased IL-1β and the effect of miR-223 on NLRP3 could be a mechanism to account for this.

Conclusions: In summary we have identifi ed an endogenous miRNA that limits NLRP3 infl ammatory capacity during myeloid differentiation, and is decreased in synovial fl uid monocytes from patients with rheumatoid or psoriatic arthritis.

Item Type:Conference Proceedings
Additional Information:Special Issue: Internal Medicine Journal, 42(Sup 1): pp. 9-10
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kurowska-Stolarska, Dr Mariola
Authors: Haneklaus, M., Gerlic, M., Kurowska-Stolarska, M., Rainey, A., Pitch, D., Hammerschmidt, W., O’Neill, L., and Masters, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Internal Medicine Journal
Publisher:Royal Australasian College of Physicians
ISSN:1444-0903
ISSN (Online):1445-5994

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