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血小板激活因子破坏鼻上皮质屏障,独立于血小板激活因子受体通路
Juan Tan1, Xinling Han1, Shenting Li1
1Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China.
血小板激活因子 (PAF) 通过激活NLRP3炎症体而不是PAF受体,在患有鼻多 (CRSwNP) 的慢性鼻炎时破坏鼻上皮质屏障. 这一发现解释了PAF受体对抗剂在临床环境中的无效性.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 鼻科 鼻科是指鼻科的专家.
背景情况:
- 血小板激活因子 (PAF) 通过影响血管透性,与鼻塞和鼻有关.
- 通过PAF影响鼻上皮质屏障的确切机制,特别是在带鼻息肉的慢性鼻炎 (CRSwNP) 中,仍然不完全理解.
研究的目的:
- 在CRSwNP的背景下,研究PAF对鼻上皮质屏障功能的影响.
- 阐明PAF受体 (PAFR) 和NLRP3炎症体在PAF介导的鼻上表皮的作用中的作用.
主要方法:
- 人鼻上皮细胞 (hNECs) 在空气-液体界面培养,并在PAF刺激之前先用PAFR抑制剂 (Apafant) 或NLRP3抑制剂 (MCC950) 进行预处理.
- 鼻上皮质屏障的完整性是通过测量跨皮质电阻 (TER) 和光素流量来评估的.
- 分析了紧结蛋白 (ZO-1,ocludin,claudin-1,claudin-4) 和炎症组分的表达水平.
主要成果:
- 在hNECs中,PAF显著降低了TER,增加了光素的透性,同时降低了紧结蛋白的表达.
- MCC950,但不是Apafant,减轻了PAF在上皮屏障上的破坏性影响.
- MCC950抑制了PAF诱导的NLRP3炎症酶的激活,包括caspase-1,ASC,IL-1β和IL-18.
结论:
- 在CRSwNP中,PAF会破坏鼻上皮质屏障,这是一种由NLRP3炎症酶激活而不是PAFR信号传递介导的过程.
- 这些发现表明NLRP3炎症酶抑制剂,而不是PAFR抗体,可能是CRSwNP的更有效的治疗策略.
- 这项研究为PAFR抗剂在临床试验中对PAF介导的鼻炎的有限疗效提供了机制性的解释.
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