Department of Respiratory Disease, Zhongshan People's Hospital, Zhongshan, Guangdong 528403, P.R. China.
Dental Implant and Restoration Centre, Zhongshan People's Hospital, Zhongshan, Guangdong 528403, P.R. China.
Mol Med Rep. 2021 Nov;24(5). doi: 10.3892/mmr.2021.12387. Epub 2021 Aug 30.
Airway epithelial cells, which are the first physical defense barrier against allergens, play a pivotal role in immunity, airway inflammation and airway remodeling. The damage and dysfunction of these cells trigger the development of airway inflammatory diseases. Exosomes, which exist in various bodily fluids, mediate cell‑cell communication and participate in the immune response process. The present study aimed to investigate whether serum exosomes play a pro‑inflammatory role in bronchial epithelial cells (BEAS‑2B cells) and, if so, explore the underlying molecular mechanisms. A guinea pig model of House dust mite (HDM)‑induced asthma was established by sensitizing the rodents with HDM and PBS, and serum‑derived exosomes were harvested. It was found that serum‑derived exosomes from HDM‑sensitized guinea pigs displayed higher levels of exosomal markers than those from controls. Additionally, western blot analysis and reverse transcription‑quantitative PCR indicated that serum‑derived exosomes from HDM‑sensitized guinea pigs carried heat shock protein 70 and triggered an inflammatory response in BEAS‑2B cells via the toll‑like receptor 4 (TLR4)‑NF‑κB pathway. However, TAK‑242, an inhibitor of the expression of TLR4, blocked the activation of the TLR4‑NF‑κB pathway. These findings provided a novel mechanism for exosome‑mediated inflammatory responses and a new perspective for the intervention of inflammatory airway disorders.
气道上皮细胞是抵御过敏原的第一道物理防御屏障,在免疫、气道炎症和气道重塑中发挥着关键作用。这些细胞的损伤和功能障碍会引发气道炎症性疾病。外泌体存在于各种体液中,介导细胞间通讯并参与免疫反应过程。本研究旨在探讨血清外泌体是否在支气管上皮细胞 (BEAS-2B 细胞) 中发挥促炎作用,如果是,探讨其潜在的分子机制。通过用 HDM 和 PBS 致敏啮齿动物建立屋尘螨 (HDM) 诱导的哮喘豚鼠模型,并提取血清衍生的外泌体。结果发现,与对照组相比,HDM 致敏豚鼠血清衍生的外泌体显示出更高水平的外泌体标志物。此外,Western blot 分析和逆转录-定量 PCR 表明,HDM 致敏豚鼠的血清衍生外泌体携带热休克蛋白 70,并通过 toll 样受体 4 (TLR4)-NF-κB 途径在 BEAS-2B 细胞中引发炎症反应。然而,TLR4 表达抑制剂 TAK-242 阻断了 TLR4-NF-κB 途径的激活。这些发现为外泌体介导的炎症反应提供了一种新的机制,并为干预炎症性气道疾病提供了新的视角。