Abstract
BackgroundThe findings of a previous study by Jin et al. have shown that microRNA (miR)-155 was upregulated in patients with acute gouty arthritis and enhanced the proinflammatory cytokines. There is no direct evidence to support that miR-155 is indeed involved in monosodium urate (MSU)-induced inflammatory responses in vivo. The aim of this study was to investigate the role of miR-155 knock-out (KO) or knock-in (KI) mice in MSU-induced animal models to mimic acute gout.MethodsMiR-155 expression in cultured bone marrow-derived macrophages (BMDMs) from miR-155 KO, miR-155 KI, and wild-type (WT) mice treated with MSU crystals in vitro was detected by real-time quantitative polymerase chain reaction (qPCR). MiR-155 KO and WT mice were used to induce an acute gouty inflammatory response with MSU crystals including models of foot pad inflammation, ankle arthritis, air pouch inflammation, and peritonitis. Furthermore, the proinflammatory interleukin (IL)-1β levels in lavage fluids from air pouch and peritoneal cavity models were measured by enzyme-linked immunosorbent assay (ELISA), and tumor necrosis factor (TNF)-α production from BMDMs of miR-155 KI mice treated with MSU were measured by flow cytometry.ResultsMiR-155 expression was quickly upregulated in BMDMs from WT mice following MSU treatment in vitro. In comparison with WT mice in vivo, the swelling index of miR-155 KO mice showed no significant difference in the murine foot pad and ankle arthritis models for the indicated different time points. There were similar changes in total cell numbers of lavage fluids in the air pouch and peritoneal cavity models between miR-155 KO and WT mice following MSU crystal injection. Moreover, the IL-1β levels of lavage fluids in the air pouch and peritonitis models from miR-155 KO mice were almost the same as those from WT mice. TNF-α levels were comparable from BMDMs treated with MSU crystals in vitro between miR-155 KI mice and WT mice.ConclusionsMiR-155 is dispensable in MSU-induced gouty inflammation in mice. Deletion of miR-155 might not be an effective therapeutic approach to relieve the inflammation in acute gout.
Highlights
The findings of a previous study by Jin et al have shown that microRNA-155 was upregulated in patients with acute gouty arthritis and enhanced the proinflammatory cytokines
The proinflammatory cytokine IL-1β levels in lavage fluids from the peritoneal cavity and air pouch models and tumor necrosis factor (TNF)-α levels from bone marrow-derived macrophages (BMDMs) of miR-155 knock-in (KI) mice treated with monosodium urate (MSU) crystals were measured
In the present study, based on the findings from Jin et al [7] who found that aberrant miR-155 expression was involved in the pathogenesis of gout, we further investigated the role of miR-155 in MSU-mediated gout using miR-155 KO or KI mice in in-vitro or in-vivo experiments
Summary
The findings of a previous study by Jin et al have shown that microRNA (miR)-155 was upregulated in patients with acute gouty arthritis and enhanced the proinflammatory cytokines. MiR-146a expression was reduced during the acute flare compared with the intercritical period in the paired samples as well as in the urate peritonitis model Those findings reflect the more complex multicellular in vivo response to MSU crystals. Jin et al [7] showed that miR-155 was upregulated in synovial fluid mononuclear cells (SFMCs) from patients with acute gouty arthritis and MSU crystals strongly induced miR-155 expression in PBMCs in vitro. MiR-155 levels in PBMCs from gout patients were comparable with healthy individuals These paradoxical data suggest that the same miRNA may play different roles in different tissues/organs and conditions. There is still a lack of direct evidence to further determine whether miR-155 is involved in MSU-induced inflammation in vivo
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