Regulation of microRNA 223 expression in a gouty arthritis

Statache, G., Rainey, A., Crawford, L., Masters, S., Balanescu, A., McInnes, I. and Kurowska-Stolarska, M. (2012) Regulation of microRNA 223 expression in a gouty arthritis. In: European Congress of Immunology, Glasgow, UK, 5-8 Sept 2012, p. 227. (doi:10.1111/imm.12002)

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Abstract

Purpose/Objective: Introduction. Gout is an inflammatory chronic disease caused by deposition of uric acid crystals in the joint and connective tissues causing pain and disability. Current data suggest that gout is mediated by IL-1b that is produced due to the activation of the inflammasome pathway by uric acid crystals.In addition, neutrophil influx in the joint is the key initiator of a gout flare. miR-223 has been identified as a masterswitch molecule limiting neutrophil activation. In addition, we showed previously that this miR negatively regulates NLRP3 (an inflammasome component) and IL-1b production in human macrophages.

Objective. To investigate miR-223 expression and regulation in monocytes and neutrophils of gout patients.

Materials and methods: Methods. CD14+ cells and neutrophils were isolated from gout patients (n = 10) and healthy donors (n = 6) peripheral blood using CD14 microbeads and polylymphoprep gradient buffer, respectively. CD14+ from healthy donors were stimulated with LPS (10 ng/ml) IL-1beta (10010 ng/ml), IL-6 (100 ng/ml), TNF alpha (10100 ng/ml) or monosodium urate crystals MSU (1 mg1 ug/ml) for different time points (2472 h). Cells were harvested and miRNA extracted. Expression of miR-223 and endogenous control snRNA U1 was assessed by qPCR.

Results: Results. miR-223 expression in peripheral blood monocytes of patients withchronic gout was lower compared to healthy controls. This suggest that overproduction of IL-1b in chronic disease might be partially mediated by low levels of miR-223. In vitro studies revealed that MSU, IL-1b, TNFa and IL-6 significantly inhibited miR- 223 expression in monocytes in all time points (2472 h). In contrast, IL-10 strongly increased miR-223 expression. Interestingly, the levels of miR-223 in peripheral blood neutrophils were higher in gout patients compared to healthy controls.

Conclusions: A decrease in miR-223 expression in monocytes of chronic gout patients may contribute to uric acid crystals induced inflammasome activation and chronicity of disease. Upregulation of miR-223 expression in gout neutrophils may reflect the activation of mechanisms that limits neutrophils activation and lead to the resolution of gout flares.

Item Type:Conference Proceedings
Additional Information:Special Issue:, 137(Sup 1): p. 227
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Statache, Mrs Gianina and Kurowska-Stolarska, Dr Mariola
Authors: Statache, G., Rainey, A., Crawford, L., Masters, S., Balanescu, A., McInnes, I., and Kurowska-Stolarska, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology
Publisher:Blackwell Publishing Ltd.
ISSN:0019-2805
ISSN (Online):1365-2567

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