Department of Clinical Laboratory Diagnostics, Medical University of Białystok, 15A Jerzego Waszyngtona St., 15-269, Białystok, Poland.
Department of Biophysics, Medical University of Białystok, Białystok, Poland.
Sci Rep. 2022 Dec 9;12(1):21375. doi: 10.1038/s41598-022-25855-2.
Activation of the nuclear factor kappa-B (NF-κB) stimulates the production of pro-inflammatory molecules involved in the formation of intracranial aneurysms (IA). The study aimed to assess the NF-κB p65 subunit and the GRO-α chemokine and its receptor CXCR2 concentrations in unruptured intracranial aneurysm patients (UIA, n = 25) compared to individuals without vascular changes in the brain (n = 10). It was also analyzed whether tested proteins are related to the size and number of aneurysms. Cerebrospinal fluid (CSF) and serum protein levels were measured using the ELISA method. Median CSF and serum NF-κB p65 concentrations were significantly lower, while median CSF GRO-α and CXCR2 concentrations were significantly higher in UIA patients compared to the control group. CSF and serum NF-κB p65 concentrations negatively correlated with the number of aneurysms. In UIA patients the median GRO-α concentration was two-fold and CXCR2 almost four-fold higher in CSF compared to the serum value. CSF GRO-α concentration positively correlated with the size of aneurysms.Significantly decreased CSF NF-κB p65 and significantly increased CSF GRO-α and its CXCR2 receptor concentrations in UIA patients compared to the control group may altogether suggest that the canonical NF-κB signaling pathway is activated and its target pro-inflammatory genes are highly expressed in UIA patients. However, to unequivocally assess the involvement of the classical NF-κB pathway with the participation of the NF-κB p65 subunit and the GRO-α/CXCR2 axis in the formation of IA, further in vivo model studies are needed.
核因子 kappa-B(NF-κB)的激活可刺激参与颅内动脉瘤(IA)形成的促炎分子的产生。本研究旨在评估未破裂颅内动脉瘤患者(UIA,n=25)与无脑部血管变化的个体(n=10)之间 NF-κB p65 亚基和 GRO-α趋化因子及其受体 CXCR2 浓度。还分析了测试蛋白是否与动脉瘤的大小和数量有关。使用 ELISA 法测量脑脊液(CSF)和血清蛋白水平。与对照组相比,UIA 患者的 CSF 和血清 NF-κB p65 浓度中位数显着降低,而 CSF GRO-α和 CXCR2 浓度中位数显着升高。CSF 和血清 NF-κB p65 浓度与动脉瘤数量呈负相关。与血清值相比,UIA 患者 CSF 中 GRO-α浓度中位数高两倍,CXCR2 浓度高近四倍。CSF GRO-α浓度与动脉瘤大小呈正相关。与对照组相比,UIA 患者 CSF 中 NF-κB p65 明显降低,CSF 中 GRO-α及其 CXCR2 受体浓度明显升高,这可能表明经典 NF-κB 信号通路在 UIA 患者中被激活,其靶促炎基因在 UIA 患者中高度表达。然而,为了明确评估经典 NF-κB 途径是否涉及 NF-κB p65 亚基和 GRO-α/CXCR2 轴参与 IA 的形成,还需要进一步的体内模型研究。