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

被引：0

作者：

Zhu, Lingjiang ^{[1
]}

Wang, Yuqi ^{[1
]}

Shan, Lizhen ^{[2
]}

Xue, Yu ^{[3
]}

Schett, Georg ^{[4
,5
]}

Herrmann, Martin ^{[4
,5
]}

Liu, Lei ^{[1
]}

机构：

[1] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Rheumatol, Hangzhou 310009, Zhejiang, Peoples R China

[2] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Endocrinol, Hangzhou 310009, Zhejiang, Peoples R China

[3] Fudan Univ, Huashan Hosp, Div Rheumatol, Shanghai 200040, Peoples R China

[4] Friedrich Alexander Univ FAU Erlangen Nurnberg, Deutsch Zentrum Immuntherapie DZI, D-90154 Erlangen, Germany

[5] Univ Klinikum Erlangen, D-90154 Erlangen, Germany

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2025年 / 1871卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Colchicine; Gout; Monosodium urate crystals; Neutrophil extracellular traps; Actin; DNASE-I; POLYMORPHONUCLEAR; MOBILITY;

D O I：

10.1016/j.bbadis.2024.167602

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-1(3 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-1(3 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-1(3 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-1(3 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.

引用

页数：9