维生素D触发hCAP18/LL-37的产生:对LL-37引起的人类骨质细胞毒性的影响
Alexandra Aidoukovitch1, Elisabeth Bankell1, Daniel Svensson1
1Department of Experimental Medical Science, Lund University, BMC D12, SE-22184, Lund, Sweden.
Biochemical and biophysical research communications
|April 20, 2024
概括
维生素D显著增强免疫细胞中抗微生物人类甲基素LL-37 (hCAP18/LL-37) 的产生. 这种增加可能有助于维生素D.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 人类甲基素LL-37具有抗微生物特性,但对宿主细胞可能具有细胞毒性.
- 该CAMP基因编码LL-37前体hCAP18,后者被加工成活性LL-37.
- 已知维生素D可刺激CAMP基因活性,但其对hCAP18/LL-37蛋白水平的影响需要进一步研究.
研究的目的:
- 研究维生素D对人类THP-1单细胞中hCAP18/LL-37蛋白质生成的影响.
- 为了确定维生素D诱导的hCAP18/LL-37生产与宿主细胞毒性的生理相关性.
主要方法:
- 定量实时PCR (RT-qPCR) 用于测量CAMP mRNA水平.
- 点点分析和ELISA以量化hCAP18/LL-37蛋白质含量.
- 用蛋白质酶抑制剂MG132治疗以评估蛋白质周转.
- 测量MTT测试以评估细胞活力.
主要成果:
- 维生素D的生理度 (50nM) 将CAMP mRNA水平提高了大约170倍.
- 维生素D刺激导致THP-1细胞溶解物中的hCAP18/LL-37蛋白含量增加了3-4倍.
- 蛋白质酶抑制提高了hCAP18/LL-37水平,表明蛋白质酶对其周转率的调节.
- 维生素D刺激细胞中产生的LL-37度 (1.04μM) 降低了人类骨质母细胞样细胞 (MG63) 的活力.
结论:
- 维生素D显著增强了人类单细胞中的hCAP18/LL-37的产生.
- 维生素D引起的hCAP18/LL-37水平的增加可能对人类骨质母细胞中LL-37介导的毒性产生生理或病理生理影响.
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