[1]吴威甫,蒋艳琼,吴 辉,等.趋化因子C-C-基元配体4通过激活人单核白血病细胞THP-1源性巨噬细胞NOD样受体热蛋白结构域相关蛋白3炎症小体促进骨关节炎发展实验研究[J].陕西医学杂志,2024,(9):1187-1192.[doi:DOI:10.3969/j.issn.1000-7377.2024.09.007]
　WU Weifu,JIANG Yanqiong,WU Hui,et al.Chemokine CCL4 induces the progression of osteoarthritis by activating NLRP3 inflammasome in THP-1-derived macrophages[J].,2024,(9):1187-1192.[doi:DOI:10.3969/j.issn.1000-7377.2024.09.007]
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趋化因子C-C-基元配体4通过激活人单核白血病细胞THP-1源性巨噬细胞NOD样受体热蛋白结构域相关蛋白3炎症小体促进骨关节炎发展实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2024年9期
页码:
1187-1192
栏目:
基础研究
出版日期:
2024-09-05

文章信息/Info

Title:
Chemokine CCL4 induces the progression of osteoarthritis by activating NLRP3 inflammasome in THP-1-derived macrophages
作者:
吴威甫1; 蒋艳琼2; 吴 辉3; 银 毅2
(1.川北医学院附属遂宁市中医院骨科,四川 遂宁 629000; 2.遂宁市中心医院骨科,四川 遂宁 629000; 3.南充市中心医院骨科,四川 南充 637000)
Author(s):
WU Weifu; JIANG Yanqiong; WU Hui; YIN Yi
(Department of Orthopedics,Suining Municipal Hospital of Traditional Chinese Medicine Affiliated to North Sichuan Medical College,Suining 629000,China)
关键词:
骨关节炎;  C-C-基元配体4;  巨噬细胞;  NOD样受体热蛋白结构域相关蛋白3;  软骨细胞;  炎症小体
Keywords:
Osteoarthritis;  C-C-motif ligand 4;  Macrophages;  NLRP3;  Chondrocytes;  Inflammasome
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2024.09.007
文献标志码:
A
摘要:
目的:探讨趋化因子C-C-基元配体4(CCL4)通过激活人单核白血病细胞THP-1源性巨噬细胞中NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体促进骨关节炎(OA)发展的潜在作用机制。方法:用CCL4和NLRP3小干扰RNA(siRNA)处理THP-1源性巨噬细胞,然后将预处理的THP-1源性巨噬细胞与软骨细胞共培养。采用流式细胞术检测细胞凋亡和活性氧(ROS); 采用酶联免疫吸附测定(ELISA)法检测白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶1(MMP-1)和MMP-13水平; 采用胶原降解试验检测胶原活性; 采用Western blot分析NLRP3和凋亡相关微粒蛋白(ASC)蛋白的表达。结果:CCL4不会诱导THP-1源性巨噬细胞凋亡,但可上调炎症因子(IL-1β和TNF-α)和炎症相关蛋白(NLRP3和ASC)的表达。将CCL4预处理的THP-1源性巨噬细胞与软骨细胞共培养可以上调软骨细胞中MMP-1和MMP-13的表达,增强胶原酶活性,促进ROS的产生及软骨细胞的凋亡。抑制NLRP3的表达可以部分逆转CCL4对炎症因子的影响,以及与THP-1源性巨噬细胞共培养的软骨细胞相关功能的影响。结论:CCL4处理的THP-1源性巨噬细胞可通过激活NLRP3加速软骨细胞OA的进展。
Abstract:
Objective:To investigate the underlying mechanisms of chemokine C-C-motif ligand 4(CCL4)induces the progression of osteoarthritis(OA)by activating NLR family pyrin domain containing 3(NLRP3)inflammasome in human monocytic leukemia cells THP-1-derived macrophages.Methods:THP-1-derived macrophages were processed with CCL4 and NLRP3 siRNA,then the pre-treated THP-1-derived macrophages were co-cultured with chondrocytes.Cell apoptosis and ROS were verified by flow cytometry.IL-1β,TNF-α,MMP-1 and MMP-13 levels were assessed by ELISA.Collagen activity was identified by collagen degradation assay.NLRP3 and ASC expressions were confirmed by Western blot.Results:CCL4 could not induce apoptosis,but upregulate inflammatory factors(IL-1β and TNF-α)and inflammation-related proteins(NLRP3 and ASC)in THP-1-derived macrophages.The co-cultivation of CCL4-treated THP-1-derived macrophages could increase MMP-1 and MMP-13 expressions,enhance collagenase activity,accelerate ROS production and apoptosis in chondrocytes.Inhibition of NLRP3 expression could partly reverse the influences of CCL4 on inflammation factors and the related functions of chondrocytes after co-culture.Conclusion:CCL4-treated THP-1-derived macrophages accelerate the progression of OA in chondrocytes by activating NLRP3.

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备注/Memo

备注/Memo:
基金项目:四川省科技计划项目(2020YFS0529)
更新日期/Last Update: 2024-09-04