Session Title: Innate Immunity and Rheumatic Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose: Gout is characterised by episodes of intense joint inflammation in response to intra-articular monosodium urate monohydrate (MSU) crystals. miR-155 is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory arthritis. Since, the functional role of miR-155 in gouty arthritis has not been defined. The aim of this study was to examine the role of miR-155 in pathogenesis of acute gouty arthritis.
Methods: Samples from 14 patients with gouty arthritis and 10 healthy controls (HCs) were obtained. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were cultured in vitro with MSU crystals, and gene expression (human miR-155 and Src homology 2-containing inositol phosphatase, SHIP-1) were assessed by real-time PCR. THP-1 cells and human monocyte-drived macropharges were stimulated by MSU crystals and/or miR-155 transfection. Whole-cell lysates were subjected to Western blot analysis. Human TNF-α and IL-1β in cell culture supernatants were measured by Luminex. Immunohistochemistry was performed on formalin-fixed gout tissues with anti–SHIP-1 Ab. Gout peritonitis mice (Male C57BL/6J) model used to analyze expressions of miR-155, SHIP-1, and inflammatory cytokines.
Results: The samples from gouty arthritis proved to be highly enriched in miR-155, with levels of expression being higher than those found in PBMC from HC. Mir-155 was found to be strongly induced by stimulation of MSU crystals after 24 hours and their expressions gradually decreased. Stimulating with MSU crystals, the level of SHIP-1 was found to be gradually decreased in according to overexpression of mir-155. miR-155 promoted MSU-induced proinflammatory cytokine production such as TNF-α and IL-1β. Consistent with in vitro observations, miR-155 expression was also elevated in gout mice model. The production of inflammatory cytokines was markedly increased in MSU crystal induced peritonitis mice.
Conclusion: Our study confirmed that overexpression of miR-155 in SFMC led to down-regulation of SHIP-1 and an increase in the production of proinflammatory cytokines.
H. M. Jin,
Y. N. Cho,
S. J. Kee,
D. J. Park,
Y. W. Park,
S. S. Lee,
T. J. Kim,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/microrna-155-as-a-proinflammatory-regulator-via-ship-1-down-regulation-in-acute-gouty-arthritis/