IL-40 在骨关节炎患者的滑液和软骨中上调,并导致体外软骨细胞表型的改变。

IF 4.9 2区 医学 Q1 Medicine
L Andrés Cerezo, A Navrátilová, M Kuklová, A Prokopcová, J Baloun, T Kropáčková, D Veigl, S Popelka, P Fulín, R Ballay, K Pavelka, J Vencovský, L Šenolt
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引用次数: 0

摘要

引言IL-40是一种与类风湿性关节炎(RA)或斯约格伦综合征等自身免疫性结缔组织疾病相关的新型细胞因子。我们以前曾研究表明,IL-40 在类风湿性关节炎关节中蓄积,并在免疫细胞和成纤维细胞中表达。因此,我们旨在评估 IL-40 在透明软骨和软骨细胞活性中的作用:采用免疫组化方法检测骨关节炎(OA)软骨加载和未加载区域配对样本(n=5)中的 IL-40。用 ELISA 方法分析了膝关节损伤后 OA(31 人)和对照组(34 人)滑膜液中的 IL-40。在体外测试了 IL-40 对软骨细胞的影响:结果:在OA软骨表层区的软骨细胞中发现了IL-40,负载和非负载活检组织中均有发现。此外,只有加载外植体的活检结果显示过渡区软骨细胞中的 IL-40 呈显著阳性。与对照组相比,OA 患者滑液中的 IL-40 水平明显升高(p 结论:与对照组相比,本研究首次证明了IL-40在OA软骨中的积累及其在OA患者滑液中的上调。此外,细胞外IL-40似乎在促进炎症和软骨破坏方面发挥了作用,促使软骨细胞的行为朝着更具侵袭性的表型发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
IL-40 is up-regulated in the synovial fluid and cartilage of osteoarthritis patients and contributes to the alteration of chondrocytes phenotype in vitro.

Introduction: IL-40 is a novel cytokine associated with autoimmune connective tissue disorders such as rheumatoid arthritis (RA) or Sjögren syndrome. We have previously shown an accumulation of IL-40 in the RA joint and its expression by immune cells and fibroblasts. Therefore, we aimed to assess the role of IL-40 in association with hyaline cartilage and chondrocyte activity.

Methods: Immunohistochemistry was employed to detect IL-40 in paired samples of loaded and unloaded regions of osteoarthritis (OA) cartilage (n=5). Synovial fluid IL-40 was analysed by ELISA in OA (n=31) and control individuals after knee injury (n=34). The impact of IL-40 on chondrocytes was tested in vitro.

Results: IL-40 was found in chondrocytes of the superficial zone of the OA cartilage, both in loaded and unloaded explants. Additionally, only biopsies from loaded explants showed significant IL-40 positivity in transitional zone chondrocytes. Levels of IL-40 were significantly elevated in the synovial fluid from OA patients compared to controls (p<0.0009) and correlated with synovial fluid leukocyte counts in OA (r=0.444, p=0.014). Chondrocytes exposed to IL-40 dose dependently increased in the secretion of pro-inflammatory cytokines IL-6 (p<0.0001) and IL-8 (p=0.004). Moreover, a dose dependent up-regulation of matrix degrading metalloproteinases MMP-1 (p=0.004), MMP-3 (p=0.031) and MMP-13 (p=0.0002) upon IL-40 treatment was observed in contrast to untreated chondrocytes.

Conclusion: This study is the first to demonstrate the accumulation of IL-40 in OA cartilage and its up-regulation in the synovial fluid of OA patients compared to controls. In addition, extracellular IL-40 appears to play a role in promoting inflammation and cartilage destruction by driving chondrocyte behaviour towards a more aggressive phenotype.

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来源期刊
CiteScore
8.60
自引率
2.00%
发文量
261
审稿时长
14 weeks
期刊介绍: Established in 1999, Arthritis Research and Therapy is an international, open access, peer-reviewed journal, publishing original articles in the area of musculoskeletal research and therapy as well as, reviews, commentaries and reports. A major focus of the journal is on the immunologic processes leading to inflammation, damage and repair as they relate to autoimmune rheumatic and musculoskeletal conditions, and which inform the translation of this knowledge into advances in clinical care. Original basic, translational and clinical research is considered for publication along with results of early and late phase therapeutic trials, especially as they pertain to the underpinning science that informs clinical observations in interventional studies.
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