细胞外腺三酸盐调节牙周带细胞的炎症反应
Maythwe Kyawsoewin1,2, Jeeranan Manokawinchoke1,2, Chutimon Termkwanchareon1,2
1Dental Stem Cell Biology Research Unit and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Journal of periodontology
|November 7, 2023
概括
由人类牙周带细胞 (HPDLCs) 释放的细胞外腺三酸盐 (eATP) 在炎症中具有双重作用. 低水平的eATP促进炎症,而高水平则减少炎症,可能有助于牙周再生.
科学领域:
- 牙周结带细胞生物学 牙周结带细胞生物学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 人类牙周带细胞 (HPDLC) 在应对机械应激和炎症等刺激时释放腺三酸盐 (ATP).
- 细胞外ATP (eATP) 影响HPDLC功能,包括免疫抑制和炎症反应.
- 脂聚糖 (LPS) 是牙周炎症的关键因素,但LPS诱导的eATP释放的机制及其在HPDLCs内的炎症级联中的作用尚不清楚.
研究的目的:
- 为了研究eATP在LPS刺激后的HPDLC炎症反应中的作用.
- 阐明炎症介导的eATP释放和HPDLCs炎症级联形成的详细机制.
主要方法:
- 用LPS和多酸:多酸 (多I:C) 刺激了HPDLCs,并量化了ATP的释放.
- 在eATP治疗后,分析了亲和抗炎标记物的基因表达.
- 纯能受体 (P2X7,P2Y1),NFκB和PKA的特定抑制剂,以及和PKC抑制剂,被用于剖析信号通路.
主要成果:
- LPS和多I:C诱导了HPDLCs显著的ATP释放.
- 低eATP度 (50μM) 调高了促炎基因 (例如,COX2,IL1B,IL6,IL8,IL12,TNFA) 的调节.
- 高eATP度 (500μM) 调高了抗炎基因 (例如IL4,IL10),这种效应被PKA激活 (佛斯科林) 模仿.
- 抑制P2X7受体和抑制NFκB阻断了eATP诱导的炎症性基因表达.
- 抑制P2Y1受体和抑制PKA抑制了eATP诱导的抗炎基因表达.
结论:
- 在对LPS的反应中,HPDLCs释放ATP,这表明eATP在牙周炎症中的作用.
- eATP在HPDLC炎症反应中表现出剂量依赖的双重功能,通过不同的信号通路起作用.
- 调节eATP信号提供了一个潜在的治疗策略,用于管理牙周炎症和促进组织再生.
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