Immunochemistry Laboratory, Butantan Institute, São Paulo, Brazil.
Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo, Brazil.
Front Immunol. 2020 Sep 18;11:2191. doi: 10.3389/fimmu.2020.02191. eCollection 2020.
Pararamosis is a disease that occurs due to contact with the hairs of the larval stage of the Brazilian moth . 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 . 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 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.
鳞毛蕨病是一种由巴西飞蛾幼虫的毛发接触引起的疾病。毒液会引起骨关节炎改变，损害软骨，类似于关节滑膜炎。因此，毛毛虫毛发中存在的毒性毒液会干扰关节中细胞的表型，导致炎症并促进组织损伤。因此，为了研究毒液引起的炎症机制，我们研究了 毛发提取物对人软骨细胞的影响。我们选择研究与骨关节炎 (OA) 和类风湿关节炎 (RA) 相关的细胞因子、趋化因子、基质金属蛋白酶 (MMPs)、补体成分、类花生酸和细胞外基质 (ECM) 成分。此外，为了测量与骨关节炎 (OA) 和类风湿关节炎 (RA) 相关的一些分子的蛋白质编码 mRNAs，我们进行了逆转录 (RT)，然后进行了定量实时 PCR (RT-qPCR)，并对软骨细胞转录组进行了 RNA 测序 (RNA-seq) 分析。在经提取物处理的细胞培养物上清液中，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) 和补体系统成分 (C3、C4 和 C5) 的含量增加。我们注意到，在提取物处理后，软骨细胞中的聚集蛋白聚糖和 II 型胶原蛋白明显减少，而 HMGB1 蛋白增加。软骨细胞转录组的 RNA-seq 分析使我们能够确定与疾病炎症过程相关的重要途径，例如炎症反应、免疫细胞趋化和细胞外基质 (ECM) 重塑。因此，这些结果表明 毛发的成分具有很强的炎症潜力，能够诱导软骨降解和 ECM 重塑，促进具有骨关节炎特征的疾病。调节被确定参与这种病理的信号通路可能是开发控制鳞毛蕨病和其他炎症性关节疾病的新治疗策略的有前途的方法。
