Colchicine inhibits monosodium urate crystal-mediated inflammation by influencing F-actin formation

Zhu L, Wang Y, Shan L, Xue Y, Schett G, Herrmann M, Liu L (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Biochimica et Biophysica Acta - Molecular Basis of Disease Elsevier

Book Volume: 1871

Article Number: 167602

Journal Issue: 3

DOI: 10.1016/j.bbadis.2024.167602

Abstract

Objectives: To understand the mechanism by which colchicine inhibits the inflammatory properties of monosodium urate (MSU) crystal deposits and tophi. Methods: We investigated the effects of colchicine on the inflammatory properties of monosodium urate (MSU) crystal deposits in several models: (i) In vitro tophus formation by MSU and neutrophils; (ii) MSU-induced peritonitis model; (iii) Alpha-1-antitrypsin-induced peritoneal MSU flare model; (iv) MSU-induced arthritis model. We measured neutrophil numbers, NET formation, IL-1β production and F-actin generation by MSU crystals. In addition, we tested the effect of actin inhibitors SMIFH2, Cytochalasin B and Latrunculin B in the models. Results: Colchicine did not affect neutrophil numbers in all these models. However, colchicine was highly effective to inhibit NET formation, IL-1β production and F-actin generation indicating less pronounced tophus formation, lower inflammatory properties of tophi and reduced conversion from G-actin into F-actin, respectively. F-actin was shown to accumulate in tophi without presence of colchicine and being resistant to degradation by DNase I. Actin inhibitors SMIFH2 and Cytochalasin B significantly reduced IL-1β and neutrophil elastase levels and mitigated MSU-induced arthritis. Conclusion: Colchicine effects on gout flares are not based on reducing neutrophil numbers but on changing the functional properties of tophi by reducing their DNase-resistant F-actin concentrations and thereby reducing the negative impact of NETs on IL-1β production and the pro-inflammatory state of tophi. Actin inhibitors may be interesting tools to convey anti-inflammatory properties and reduction of flares in gout patients.

Authors with CRIS profile

Georg Schett Lehrstuhl für Innere Medizin III Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Second Affiliated Hospital of Zhejiang University (SAHZU) / 浙江大学 医学院 附属第二医院 CN China (CN) Fudan University / 复旦大学 CN China (CN)

How to cite

APA:

Zhu, L., Wang, Y., Shan, L., Xue, Y., Schett, G., Herrmann, M., & Liu, L. (2025). Colchicine inhibits monosodium urate crystal-mediated inflammation by influencing F-actin formation. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1871(3). https://doi.org/10.1016/j.bbadis.2024.167602

MLA:

Zhu, Lingjiang, et al. "Colchicine inhibits monosodium urate crystal-mediated inflammation by influencing F-actin formation." Biochimica et Biophysica Acta - Molecular Basis of Disease 1871.3 (2025).

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