Bengts Sophy, Shamoun Levar, Kunath Anne, Appelgren Daniel, Welander Martin, Björck Martin, Wanhainen Anders, Wågsäter Dick
Division of Drug Research, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Division of Medical Diagnostics, Department of Laboratory Medicine, Jönköping County, Jönköping, Sweden.
J Vasc Res. 2020;57(4):236-244. doi: 10.1159/000507667. Epub 2020 May 20.
Interleukin (IL)-32 is a pro-inflammatory cytokine not previously studied in relation to abdominal aortic aneurysm (AAA). The aim of this study was to elucidate the expression and localization of IL-32 in AAA.
Expression and localization of IL-32 in human aortic tissue was studied with immunohistochemical analysis and Western blot (AAA: n = 5; controls: n = 4). ELISA was used to measure IL-32 in human plasma samples (AAA: n = 140; controls: n = 37) and in media from cultured peripheral blood mononuclear cells (PBMCs) from 3 healthy donors. IL-32 mRNA in PBMCs, endothelial cells, aortic smooth muscle cells (SMCs), and aortic tissue samples of AAA (n = 16) and control aortas (n = 9) was measured with qPCR.
IL-32 was predominantly expressed in SMCs and T-cell-rich areas. Highest mRNA expression was observed in the intima/media layer of the AAA. A weaker protein expression was detected in non-aneurysmal aortas. Expression of IL-32 was confirmed in isolated T cells, macrophages, endothelial cells, and SMCs, where expression was also inducible by cytokines such as interferon-γ. There was no difference in IL-32 expression in plasma between patients and controls.
IL-32 signaling is altered locally in AAA and could potentially play an important role in aneurysm development. Further studies using animal models would be helpful to study its potential role in AAA disease.
白细胞介素(IL)-32是一种促炎细胞因子,此前尚未针对腹主动脉瘤(AAA)进行研究。本研究的目的是阐明IL-32在AAA中的表达及定位。
采用免疫组织化学分析和蛋白质印迹法研究人主动脉组织中IL-32的表达及定位(AAA组:n = 5;对照组:n = 4)。酶联免疫吸附测定(ELISA)用于检测人血浆样本(AAA组:n = 140;对照组:n = 37)以及来自3名健康供体的培养外周血单个核细胞(PBMC)培养基中的IL-32。采用定量聚合酶链反应(qPCR)检测AAA(n = 16)和对照主动脉(n = 9)的PBMC、内皮细胞、主动脉平滑肌细胞(SMC)及主动脉组织样本中的IL-32 mRNA。
IL-32主要在内皮细胞和平滑肌细胞以及富含T细胞的区域表达。在AAA的内膜/中膜层观察到最高的mRNA表达。在非动脉瘤性主动脉中检测到较弱的蛋白表达。在分离的T细胞、巨噬细胞、内皮细胞和平滑肌细胞中证实了IL-32的表达,其表达也可被细胞因子如干扰素-γ诱导。患者与对照组血浆中IL-32的表达无差异。
IL-32信号在AAA中局部发生改变,可能在动脉瘤形成中起重要作用。使用动物模型进行进一步研究将有助于探讨其在AAA疾病中的潜在作用。