胡椒碱通过抑制NF-κB抑制类风湿关节炎患者炎性成纤维细胞样滑膜细胞

IF 3.7 4区 医学 Q2 CELL BIOLOGY
Qoyama Noel Baito, Halmat M. Jaafar, Talar Ahmad Merza Mohammad
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引用次数: 0

摘要

类风湿性关节炎(RA)是一种常见的自身免疫性疾病,由滑膜细胞增生和慢性关节炎症引起。成纤维细胞样滑膜细胞(FLSs)的激活是RA的主要特征之一,可引发炎症,导致关节软骨和关节破坏。NF-κB信号级联的异常激活被发现是FLSs的高增殖和缺陷性凋亡以及随后RA炎症的原因。胡椒碱是胡椒属植物的主要成分,常用作抗肿瘤和抗炎的天然化合物。在本研究中,我们旨在通过抑制NF-κB来评估胡椒碱对RA-FLS的抗炎作用。从68名RA患者和30名健康对照中分离出FLS,并暴露于胡椒碱。主要检测方法为MTT法、流式细胞仪、PI染色、逆转录聚合酶链式反应(RT-PCR)和ELISA。此外,哌啶在体外直接降低了NF-kB的磷酸化和NF-κB靶基因的表达,这些靶基因与RA FLSs增殖(c-Myc和Cycline D1)、细胞凋亡抑制(Bcl2和Bcl-xl)和炎症(COX2、IL-1β、TNF-α、IL-6、CCL5和CXCL10)有关,同时增加了细胞凋亡相关基因(Bax)的表达。胡椒碱还降低了FLSs分泌的细胞因子和趋化因子的蛋白质水平,这是NF-κB抑制的结果。总之,我们的研究结果通过抑制FLSs中的NF-κB途径为哌啶的抗炎能力提供了证据,提出该化合物是化学治疗RA的合适替代品。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Piperine suppresses inflammatory fibroblast-like synoviocytes derived from rheumatoid arthritis patients Via NF-κB inhibition

Rheumatoid Arthritis (RA) is a common autoimmune disease recognized by hyperplasia of synoviocytes and chronic joint inflammation. Activation of fibroblast-like synoviocytes (FLSs) is one of the main features of RA which can trigger inflammation leading to articular cartilage and joint destruction. Aberrant activation of NF-κB signaling cascade was found to be responsible for the high proliferation and defective apoptosis of FLSs and subsequent inflammation in RA. Piperine is a principal constituent of piper species frequently used as antitumor and anti-inflammatory natural compound. In this study we aimed to assess the anti-inflammatory effect of piperine on RA-FLS through NF-κB inhibition.

FLSs were isolated from 68 RA patients and 30 healthy controls and were exposed to piperine. The main assays were MTT assay, flow cytometric analysis, PI staining, reverse transcription-PCR (RT-PCR), and ELISA.

Results showed that piperine can induce the apoptosis and reduce the proliferation of RA-FLSs in vitro. Moreover, piperine directly reduced the phosphorylation of NF-kB and the expression of NF-κB target genes related to RA-FLSs proliferation (c-Myc and Cycline D1), apoptosis inhibition (Bcl2 and Bcl-xl) and inflammation (COX2, IL-1β, TNF-α,IL-6, CCL5 and CXCL10) while increasing the expression of apoptosis related ones (Bax) in vitro. Piperine also reduced the protein levels of cytokines and chemokines secreted by FLSs as a result of NF-κB inhibition.

In conclusion, our results provide evidence for the anti-inflammatory capacity of piperine through inhibition of NF-κB pathway in FLSs proposing this compound as a suitable alternative for chemical treatment of RA.

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来源期刊
Cellular immunology
Cellular immunology 生物-免疫学
CiteScore
8.20
自引率
2.30%
发文量
102
审稿时长
30 days
期刊介绍: Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.
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