血细胞高度表达的E型前列腺体受体在Crassostrea gigas的免疫反应期间调节TNF表达
Xuemei Cheng1, Weilin Wang1, Miren Dong1
1Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Dalian Key Laboratory of Aquatic Animal Disease Prevention and Control, Dalian Ocean University, Dalian, 116023, China.
Fish & shellfish immunology
|January 1, 2025
概括
研究人员在中发现了一种EP4受体同类物 (CgEP4),对免疫反应至关重要. 这项研究揭示了CGEP4通过血细胞中的MAPK通路调节瘤亡因子 (TNF),为软体动物免疫提供了洞察力.
科学领域:
- 海洋生物学 海洋生物学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 前列腺素E2 (PGE2) 通过E型前列腺素 (EP) 受体产生各种生理作用.
- 已知EP4受体在哺乳动物单细胞和巨细胞中调解免疫反应.
- 软体动物中EP4受体的功能,特别是在免疫反应中,仍然在很大程度上没有特征.
研究的目的:
- 在Crassostrea gigas.中识别和表征一个EP4受体同类.
- 研究这种EP4受体 (CgEP4) 在先天免疫反应中的作用.
- 探索血细胞中由CGEP4调节的信号通路和分子机制.
主要方法:
- 在Crassostrea gigas.中对CGEP4的鉴定和遗传学分析.
- 在HEK293细胞中CgEP4的功能表达以评估其对PGE2.2的反应.
- 在不同的组织和血细胞亚群中分析CgEP4mRNA表达.
- 通过细菌 (Vibrio splendidus) 刺激对CGEP4表达变化的研究.
- 在体内实验评估PGE2和EP4抗剂 (Grapiprant) 对血细胞中MAPK通路激活 (p-JNK,p-ERK) 和TNF表达的影响.
主要成果:
- 确定了一种具有典型EP4结构特征的CgEP4同类物,并表明它与脊椎动物EP4受体有基因关系.
- 在HEK293细胞中表达的CgEP4通过增加细胞内Ca2+水平而不是cAMP水平对PGE2作出反应.
- CgEP4 mRNA主要表达在血细胞中,特别是在农核细胞中.
- 细菌刺激导致了血细胞中CgEP4mRNA的显著上调.
- 活体内PGE2治疗抑制了JNK酸化和降低了TNF表达,这种效应被EP4抗剂逆转.
- 在的天生的免疫力中,CGEP4通过MAPK通路调节TNF表达.
结论:
- 这项研究提供了第一个实验证据,证明了Crassostrea gigas.中的软体动物功能EP4受体CgEP4的存在.
- 在先天免疫反应过程中,CGEP4参与通过基激活蛋白激酶 (MAPK) 途径调节瘤亡因子 (TNFs) 的表达.
- CgEP4作为一种潜在的表面标记物,用于识别和分类血细胞内的特定亚粒细胞群.
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