Dieckol ameliorates inflammatory response via inhibition of CHI3L1 expression in collagen-induced arthritis rats.

IF 2.5 4区 医学 Q3 ALLERGY
Allergologia et immunopathologia Pub Date : 2025-05-01 eCollection Date: 2025-01-01 DOI:10.15586/aei.v53i3.1308
Weijiang Wang, Huijie Li
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引用次数: 0

Abstract

Background: Dieckol (DEK), the main phlorotannin of brown algal, has been regarded as a powerful anti-inflammatory agent in various diseases. Rheumatoid arthritis (RA) is a typical inflammatory autoimmune disease affecting synovial joints. However, the pharmaceutical effect of DEK on RA is still waiting to be unveiled.

Methods: A collagen-induced arthritis (CIA) rat model was established and DEK was administered intraperitoneally for three weeks. Paw swelling and histologic analysis were performed to evaluate CIA progression. Inflammatory cytokine and oxidative biomarker expression were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Vascular endothelial growth factor A (VEGFA) expression in synovial joint was assessed by immunoblotting and immunofluorescent (IF) staining. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to evaluate chondrocyte apoptosis. Western blot assay was performed to determine the expression level of nuclear erythroid-derived 2-like 2 (Nrf2), chitinase 3-like protein 1(CHI3L1) and apoptosis-specific proteins. Finally, CHI3L1 overexpression was used to explore its essential role in the biological effect of DEK in vivo.

Results: DEK treatment significantly ameliorates paw swelling, inflammatory cell infiltration, chondrocyte apoptosis and vascular pannus formation in CIA rats. Moreover, inflammatory cytokine and oxidative biomarker expression was also attenuated by DEK treatment. Notably, DEK treatment obviously promoted Nrf2 nuclear import and CHI3L1 expression in synovial joint. Overexpression of CHI3L1 by AVV-mediated transfection abrogated the pharmaceutical effect of DEK in vivo.

Conclusion: This study provides a promising translational potential of DEK as an anti-rheumatic drug facilitating RA clinical treatment.

Dieckol通过抑制胶原诱导关节炎大鼠的CHI3L1表达来改善炎症反应。
背景:褐藻中主要的绿皮素二酚(DEK)被认为是治疗多种疾病的有效抗炎剂。类风湿性关节炎(RA)是一种典型的影响滑膜关节的炎症性自身免疫性疾病。然而,DEK对RA的药物作用尚待揭示。方法:建立胶原性关节炎(CIA)大鼠模型,给予DEK腹腔注射3周。进行足部肿胀和组织学分析以评估CIA进展。采用实时定量聚合酶链反应(RT-qPCR)和酶联免疫吸附试验(ELISA)检测炎症细胞因子和氧化生物标志物的表达。采用免疫印迹法和免疫荧光法检测滑膜关节血管内皮生长因子A (VEGFA)的表达。采用tdt介导的dUTP镍端标记(TUNEL)染色评价软骨细胞凋亡。Western blot检测核红细胞衍生2-样2 (Nrf2)、几丁质酶3-样蛋白1(CHI3L1)和凋亡特异性蛋白的表达水平。最后,我们利用CHI3L1过表达来探讨其在DEK体内生物学效应中的重要作用。结果:DEK治疗可显著改善CIA大鼠足跖肿胀、炎症细胞浸润、软骨细胞凋亡和血管管形成。此外,DEK治疗也降低了炎症细胞因子和氧化生物标志物的表达。值得注意的是,DEK治疗明显促进了滑膜关节Nrf2核的输入和CHI3L1的表达。通过avv介导的转染过表达CHI3L1,可以消除DEK在体内的药物作用。结论:本研究为DEK作为抗风湿病药物促进RA临床治疗提供了良好的转化潜力。
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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
131
审稿时长
6-12 weeks
期刊介绍: Founded in 1972 by Professor A. Oehling, Allergologia et Immunopathologia is a forum for those working in the field of pediatric asthma, allergy and immunology. Manuscripts related to clinical, epidemiological and experimental allergy and immunopathology related to childhood will be considered for publication. Allergologia et Immunopathologia is the official journal of the Spanish Society of Pediatric Allergy and Clinical Immunology (SEICAP) and also of the Latin American Society of Immunodeficiencies (LASID). It has and independent international Editorial Committee which submits received papers for peer-reviewing by international experts. The journal accepts original and review articles from all over the world, together with consensus statements from the aforementioned societies. Occasionally, the opinion of an expert on a burning topic is published in the "Point of View" section. Letters to the Editor on previously published papers are welcomed. Allergologia et Immunopathologia publishes 6 issues per year and is included in the major databases such as Pubmed, Scopus, Web of Knowledge, etc.
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