Related Experiment Video
Updated: Aug 15, 2026
Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
microRNA-223 Deficiency Exacerbates Acute Inflammatory Response to Monosodium Urate Crystals by Targeting NLRP3
Qi-Bin Yang1,2, Ling-Qin Li1, Quan-Bo Zhang2,3
1Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan Province, People's Republic of China.
Objective:
MicroRNAs were identified as master-switch molecules limiting acute inflammatory response. This study investigated the potential role of microRNA (miR)-223 in the mechanism of gout.
Methods:
Wild-type (WT) and miR-223 knock-out (KO) mice were used to evaluate the phenotypes of gout models. Inflammatory cytokines were measured in air pouch and peritoneal cavity lavage fluid. In addition to miR-223 level in gout patients, miR-223 and pro-inflammatory genes were examined in bone marrow-derived macrophages (BMDMs) from mice as well as peripheral blood mononuclear cells from healthy controls (HC) treated with monosodium urate (MSU) crystals in vitro.
Results:
MiR-223 was up-regulated in the early phase in BMDMs from WT mice after MSU challenge and decreased rapidly, and this was not observed in miR-223 KO mice in vitro. In addition, miR-223 was required for macrophages homeostasis. In comparison with WT mice in vivo, miR-223 deficiency exacerbated swelling index of MSU-induced inflammation in foot pad and ankle joint models. MiR-223 deficiency also markedly aggravated inflammatory cells infiltration and cytokines release including interleukin (IL)-1β, IL-6 and monocyte chemotactic protein-1 (MCP-1) in the air pouch and peritonitis models. In the in vitro experiments, miR-223 deficiency promoted the inflammatory response by targeting NLR family pyrin domain containing protein 3 (NLRP3). Besides, miR-223 level was down-regulated in gout patients and in HC exposed to MSU in vitro.
Conclusion:
MiR-223 was down-regulated in gout patients and miR-223 deficiency exacerbated inflammatory response in diverse murine models, suggesting that up-regulation of miR-223 could be a potential therapeutic strategy for alleviating gouty inflammation.
Insights
MicroRNA-223 plays a crucial role in regulating gout inflammation. Lower levels of microRNA-223 are found in gout patients, and its deficiency worsens inflammatory responses, suggesting therapeutic potential.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of inflammatory responses.
- Gout is a type of inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals.
- The specific role of miR-223 in gout pathogenesis remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of microRNA (miR)-223 in the mechanism of gout.
- To determine the expression levels of miR-223 in gout patients and in response to MSU crystal challenge.
- To evaluate the impact of miR-223 deficiency on gouty inflammation in mouse models.
Main Methods:
- Utilized wild-type (WT) and miR-223 knock-out (KO) mice to model gout.
- Assessed inflammatory cytokine levels in various lavage fluids.
- Examined miR-223 expression and pro-inflammatory gene activity in mouse bone marrow-derived macrophages (BMDMs) and human peripheral blood mononuclear cells (PBMCs) in vitro following MSU stimulation.
Main Results:
- MiR-223 expression was transiently upregulated in WT BMDMs post-MSU challenge but absent in KO mice.
- miR-223 deficiency exacerbated MSU-induced swelling, inflammatory cell infiltration, and cytokine release (IL-1β, IL-6, MCP-1) in vivo.
- In vitro, miR-223 deficiency promoted inflammation by targeting NLRP3, and miR-223 levels were downregulated in gout patients and MSU-treated healthy controls.
Conclusions:
- MiR-223 is downregulated in gout patients.
- miR-223 deficiency exacerbates gouty inflammation through various mechanisms.
- Upregulation of miR-223 presents a potential therapeutic strategy for gouty inflammation.
