Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy.
Department of Medical Science, University of Ferrara, Ferrara, Italy.
Mediators Inflamm. 2018 Jul 26;2018:9629537. doi: 10.1155/2018/9629537. eCollection 2018.
"Oxinflammation" is a recently coined term that defines the deleterious crosstalk between inflammatory and redox systemic processes, which underlie several diseases. Oxinflammation could be latently responsible for the predisposition of certain healthy individuals to disease development. The oxinflammatory pathway has been recently suggested to play a crucial role in regulating the activity of TNF-related apoptosis-inducing ligand (TRAIL), a TNF superfamily member that can mediate multiple signals in physiological and pathological processes. Therefore, we investigated the associations between TRAIL and key players of vascular redox homeostasis.
We measured circulating TRAIL levels relative to praoxonas-1, lipoprotein phospholipase-A2, and ceruloplasmin levels in a cohort of healthy subjects ( = 209).
Multivariate analysis revealed that ceruloplasmin levels were significantly inversely associated with TRAIL levels ( = -0.431, < 0.001). The observed association retained statistical significance after adjustment for additional confounding factors. After stratification for high-sensitivity C-reactive protein levels, the inverse association between TRAIL and ceruloplasmin levels remained strong and significant ( = -0.508, < 0.001, = 0.260) only in the presence of inflammation, confirming the role of inflammation as emerged in experiments where recombinant TRAIL decreased ceruloplasmin expression levels in TNF-treated PBMC cultures.
The results indicated that in an inflammatory milieu, TRAIL downregulates ceruloplasmin expression, highlighting a signaling axis involving TRAIL and ceruloplasmin that are linked via inflammation and providing important insights with potential clinical implications.
“氧化炎症”是一个最近创造的术语，它定义了炎症和氧化还原系统过程之间的有害串扰，这些过程是几种疾病的基础。氧化炎症可能是某些健康个体易患疾病的潜在原因。最近有人提出，氧化炎症途径在调节肿瘤坏死因子相关凋亡诱导配体（TRAIL）的活性方面起着至关重要的作用，TRAIL 是 TNF 超家族的一个成员，它可以在生理和病理过程中传递多种信号。因此，我们研究了 TRAIL 与血管氧化还原稳态关键因子之间的关系。
我们在一组健康受试者（n=209）中测量了循环 TRAIL 水平与 praoxonas-1、脂蛋白磷脂酶 A2 和铜蓝蛋白水平的相关性。
多变量分析显示，铜蓝蛋白水平与 TRAIL 水平呈显著负相关（=-0.431，<0.001）。在调整了其他混杂因素后，观察到的相关性仍然具有统计学意义。在高敏 C 反应蛋白水平分层后，TRAIL 和铜蓝蛋白水平之间的负相关性在炎症存在时仍然很强且具有统计学意义（=-0.508，<0.001，=0.260），仅在炎症存在时，这证实了炎症作为实验中的作用，其中重组 TRAIL 降低了 TNF 处理的 PBMC 培养物中铜蓝蛋白的表达水平。
结果表明，在炎症环境中，TRAIL 下调铜蓝蛋白的表达，突出了涉及 TRAIL 和铜蓝蛋白的信号轴，该信号轴通过炎症联系在一起，并提供了具有潜在临床意义的重要见解。
