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Human Chondrocyte Activation by Toxins From Premolis semirufa, an Amazon Rainforest Moth Caterpillar: Identifying an Osteoarthritis Signature
Frontiers in Immunology ( IF 7.3 ) Pub Date : 2020-08-11 , DOI: 10.3389/fimmu.2020.02191
Isadora M. Villas-Boas , Giselle Pidde , Flavio Lichtenstein , Ana Tung Ching Ching , Inácio de Loiola Meirelles Junqueira-de-Azevedo , Carlos DeOcesano-Pereira , Carlos Eduardo Madureira Trufen , Ana Marisa Chudzinski-Tavassi , Kátia Luciano Pereira Morais , Denise V. Tambourgi

Pararamosis is a disease that occurs due to contact with the hairs of the larval stage of the Brazilian moth Premolis semirufa. Envenomation induces osteoarticular alterations with cartilage impairment that resembles joint synovitis. Thus, the toxic venom present in the caterpillar hairs interferes with the phenotype of the cells present in the joints, resulting in inflammation and promoting tissue injury. Therefore, to address the inflammatory mechanisms triggered by envenomation, we studied the effects of P. semirufa hair extract on human chondrocytes. We have selected for the investigation, cytokines, chemokines, matrix metalloproteinases (MMPs), complement components, eicosanoids, and extracellular matrix (ECM) components related to OA and RA. In addition, for measuring protein-coding mRNAs of some molecules associated with osteoarthritis (OA) and rheumatoid arthritis (RA), reverse transcription (RT) was performed followed by quantitative real-time PCR (RT-qPCR) and we performed the RNA-sequencing (RNA-seq) analysis of the chondrocytes transcriptome. In the supernatant of cell cultures treated with the extract, we observed increased IL-6, IL-8, MCP-1, prostaglandin E2, metalloproteinases (MMP-1, MMP-2, MMP-3 and MMP-13), and complement system components (C3, C4, and C5). We noticed a significant decrease in both aggrecan and type II collagen and an increase in HMGB1 protein in chondrocytes after extract treatment. RNA-seq analysis of the chondrocyte transcriptome allowed us to identify important pathways related to the inflammatory process of the disease, such as the inflammatory response, chemotaxis of immune cells and extracellular matrix (ECM) remodeling. Thus, these results suggest that components of Premolis semirufa hair have strong inflammatory potential and are able to induce cartilage degradation and ECM remodeling, promoting a disease with an osteoarthritis signature. Modulation of the signaling pathways that were identified as being involved in this pathology may be a promising approach to develop new therapeutic strategies for the control of pararamosis and other inflammatory joint diseases.



中文翻译:

人软骨细胞被Premolis semirufa(一种亚马逊雨林蛾毛虫)中的毒素激活:鉴定骨关节炎的特征

寄生虫是一种由于与巴西蛾的幼虫期的头发接触而发生的疾病 前半乳。毒化诱导骨关节改变,软骨损伤类似于关节滑膜炎。因此,毛虫毛发中存在的有毒毒液会干扰关节中存在的细胞的表型,从而导致炎症并促进组织损伤。因此,为了解决由毒化引起的炎症机制,我们研究了P半rufa人软骨细胞上的头发提取物。我们选择了与OA和RA相关的细胞因子,趋化因子,基质金属蛋白酶(MMP),补体成分,类二十烷酸和细胞外基质(ECM)成分进行研究。此外,为测量与骨关节炎(OA)和类风湿性关节炎(RA)相关的某些分子的蛋白质编码mRNA,先进行逆转录(RT),然后进行实时定量PCR(RT-qPCR),然后进行RNA-软骨细胞转录组的测序(RNA-seq)分析。在用提取物处理的细胞培养上清液中,我们观察到IL-6,IL-8,MCP-1,前列腺素E2,金属蛋白酶(MMP-1,MMP-2,MMP-3和MMP-13)和补体的表达增加系统组件(C3,C4和C5)。我们注意到提取物处理后软骨细胞中的聚集蛋白聚糖和II型胶原蛋白均显着减少,HMGB1蛋白增加。软骨细胞转录组的RNA序列分析使我们能够确定与疾病的炎症过程相关的重要途径,例如炎症反应,免疫细胞的趋化性和细胞外基质(ECM)重塑。因此,这些结果表明前半乳头发具有很强的发炎潜能,能够诱导软骨退化和ECM重塑,从而促进具有骨关节炎特征的疾病。被鉴定为参与该病理学的信号通路的调节可能是开发用于控制寄生虫和其他炎性关节疾病的新治疗策略的有前途的方法。

更新日期:2020-09-20
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