ArticleArthritis research & therapy2013
Modulation of monosodium urate crystal-induced responses in neutrophils by the myeloid inhibitory C-type lectin-like receptor: potential therapeutic implications.
Article in Arthritis research & therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 50 citations in OpenAlex.
- A skin-kidney neutrophil axis links ultraviolet exposure to renal angiogenesis and tissue remodeling in healthy and lupus kidneys.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Targeting Inflammation in Type 2 Diabetes: The Role of Colchicine.Current diabetes reviews · 2026Review
- CLEC12A signaling represses protective immune responses and contributes to hippocampal pathology in neurotropic picornavirus infection.Scientific reports · 2025Article
- Identification of autoantibodies targeting citrullinated CLEC12A in rheumatoid arthritis patients.Journal of translational autoimmunity · 2025Article
- Non-Anticoagulation Strategies Aimed at Primary Stroke Prevention in Nascent Atrial Fibrillation.Biomedicines · 2025Review
- Unveiling the potential of CLL-1: a promising target for AML therapy.Biomarker research · 2025Review
- Emerging insights into the role of IL-1 inhibitors and colchicine for inflammation control in type 2 diabetes.Diabetology & metabolic syndrome · 2024Review
- Clec12a inhibits MSU-induced immune activation through lipid raft expulsion.Life science alliance · 2023Article
- Behçet syndrome: The disturbed balance between anti- (CLEC12A, CLC) and proinflammatory (IFI27) gene expressions.Immunity, inflammation and disease · 2023Article
- Identification of two early blood biomarkers ACHE and CLEC12A for improved risk stratification of critically ill COVID-19 patients.Scientific reports · 2023Article
- Evaluation of periodontal status and cytokine response in children with familial Mediterranean fever or systemic juvenile idiopathic arthritis.Clinical oral investigations · 2023Article
- Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review.Acta pharmacologica Sinica · 2022Review
- Regulation of the Expression, Oligomerisation and Signaling of the Inhibitory Receptor CLEC12A by Cysteine Residues in the Stalk Region.International journal of molecular sciences · 2021Article
- Expression of the myeloid inhibitory receptor CLEC12A correlates with disease activity and cytokines in early rheumatoid arthritis.Scientific reports · 2021Article
- The Inhibitory Receptor CLEC12A Regulates PI3K-Akt Signaling to Inhibit Neutrophil Activation and Cytokine Release.Frontiers in immunology · 2021Article
- Phosphoproteomic Analysis of Rat Neutrophils Shows the Effect of Intestinal Ischemia/Reperfusion and Preconditioning on Kinases and Phosphatases.International journal of molecular sciences · 2020Article
- Targeting Immunophenotypic Markers on Leukemic Stem Cells: How Lessons from Current Approaches and Advances in the Leukemia Stem Cell (LSC) Model Can Inform Better Strategies for Treating Acute Myeloid Leukemia (AML).Cold Spring Harbor perspectives in medicine · 2020Review
- C-Type Lectin-Like Receptors: Head or Tail in Cell Death Immunity.Frontiers in immunology · 2020Review
- Targeting CLL-1 for acute myeloid leukemia therapy.Journal of hematology & oncology · 2019Review
- ABCG2 contributes to the development of gout and hyperuricemia in a genome-wide association study.Scientific reports · 2018Article
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9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMonosodium urate crystals (MSU), the etiological agent of gout, are one of the most potent proinflammatory stimuli for neutrophils. The modulation of MSU-induced neutrophil activation by inhibitory receptors remains poorly characterized. The expression of the myeloid inhibitory C-type lectin-like receptor (MICL) in neutrophils is downregulated by several proinflammatory stimuli, suggestive of a role for this receptor in neutrophil function. We thus investigated the potential role of MICL in MSU-induced neutrophil activation.
methodsThe expression of MICL was monitored in human neutrophils by flow cytometry and Western blot analysis after stimulation with MSU. Protein tyrosine phosphorylation was also assessed by Western blot analysis and the production of IL-1 and IL-8 by enzyme-linked immunosorbent assay. Changes in the concentration of cytoplasmic free calcium were monitored with the Fura-2-acetoxymethyl ester calcium indicator. MICL expression was modulated with an anti-MICL antibody in neutrophils and siRNA in the PLB-985 neutrophil-like cell line.
resultsMSU induced the downregulation of MICL expression in neutrophils. A diminution in the expression of MICL induced by antibody cross-linking or siRNA enhanced the MSU-dependent increase in cytoplasmic calcium levels, protein tyrosine phosphorylation and IL-8 but not IL-1 production. Pretreatment of neutrophils with colchicine inhibited the MSU-induced downregulation of MICL expression.
conclusionsOur findings strongly suggest that MICL acts as an inhibitory receptor in human neutrophils since the downregulation of MICL expression enhances MSU-induced neutrophil activation. Since MSU downregulates the expression of MICL, MICL may play a pathogenic role in gout by enhancing neutrophil effector functions. In support of this notion, colchicine counteracts the MSU-induced loss of MICL expression. Our findings thus also provide further insight into the potential molecular mechanisms behind the anti-inflammatory properties of this drug.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.