High-density lipoproteins downregulate CCL2 production in human fibroblast-like synoviocytes stimulated by urate crystalsReportar como inadecuado




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Arthritis Research and Therapy

, 12:R23

First Online: 11 February 2010Received: 29 July 2009Revised: 22 January 2010Accepted: 11 February 2010

Abstract

IntroductionTo investigate whether monosodium urate MSU crystals induce the production of CCL2 monocyte chemoattractant protein-1; MCP-1 in human fibroblast-like synoviocytes FLS and whether this mechanism would be affected by high-density lipoproteins HDL.

MethodsHuman FLS isolated from synovial tissue explants were stimulated with MSU crystals 0.01 to 0.5 mg-ml or interleukin IL-1β 10 pg-ml in the presence or absence of HDL 50 and 100 μg-ml. The production and expression of CCL2 was evaluated with ELISA, confocal microscopy, immunofluorescence microscopy, chemotaxis assay, and real-time quantitative PCR.

ResultsExposure of FLS to MSU crystals induced CCL2 accumulation in culture medium in a dose- and time-dependent manner, reaching a plateau at 50 to 75 μg-ml MSU crystals and 20 to 24 hours. Although low, the induced CCL2 levels were sufficient to trigger mononuclear cell migration. In resting FLS, CCL2 was localized in small cytoplasmic vesicles whose number diminished with MSU crystal stimulation. Concomitantly, MSU crystals triggered the induction of CCL2 mRNA expression. All these processes were inhibited by HDL, which cause a 50% decrease in CCL2 mRNA levels and a dose-dependent inhibition of the release of CCL2. Similar results were obtained when FLS were pretreated with HDL and washed before activation by MSU crystals or IL-1β, suggesting a direct effect of HDL on the FLS activation state.

ConclusionsThe present results demonstrate that MSU crystals induce FLS to release CCL2 that is stored in vesicles in resting conditions. This mechanism is inhibited by HDL, which may limit the inflammatory process by diminishing CCL2 production and, in turn, monocytes-macrophages recruitment in joints. This study confirms the antiinflammatory functions of HDL, which might play a part in the limitation of acute gout attack.

AbbreviationsFLSfibroblast-like synoviocytes

HDLhigh-density lipoproteins

MSUmonosodium urate.

Electronic supplementary materialThe online version of this article doi:10.1186-ar2930 contains supplementary material, which is available to authorized users.

Danielle Burger and Leonardo Punzi contributed equally to this work.

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Autor: Anna Scanu - Francesca Oliviero - Lyssia Gruaz - Paolo Sfriso - Assunta Pozzuoli - Federica Frezzato - Carlo Agostini - Dan

Fuente: https://link.springer.com/







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