Department of Medicine, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Rheumatology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands; Nijmegen Institute for Infection, Inflammation and Immunity, 6500 HB Nijmegen, The Netherlands.
Cytokine. 2013 Oct;64(1):433-40. doi: 10.1016/j.cyto.2013.05.002. Epub 2013 May 30.
IL-32 has been previously shown to promote inflammation in rheumatoid arthritis patients and to contribute to IL-1β-induced ICAM-1 as well as other proinflammatory cytokines synthesis in human umbilical endothelial cells (HUVECs). Given the high rate of atherosclerosis in RA, these observations suggest that IL-32 may be involved in the inflammatory pathways of atherosclerosis.
mRNA and protein levels of IL-32 were determined in human atherosclerotic arterial vessel wall tissue by quantitative real-time PCR and immunohistochemistry. HUVEC and M1/M2 macrophages were stimulated with proinflammatory cytokines and TLR ligands to assess IL-32 mRNA induction. Human THP1 macrophages were transduced with AdIL-32γ, to investigate induction of several proatherosclerotic mediators. Finally, aortas from IL-32γ transgenic mice were studied and compared with aortas from age-matched wild-type mice.
IL-32 expression was detectable in human atherosclerotic arterial vessel wall, with the expression of IL-32β and IL-32γ mRNA significantly enhanced. TLR3-ligand Poly I:C in combination with IFNγ were the most potent inducers of IL-32 mRNA expression in both HUVEC and M1/M2 macrophages. Adenoviral overexpression of IL-32γ in human THP1 macrophages resulted in increased production of CCL2, sVCAM-1, MMP1, MMP9, and MMP13. The IL-32γ transgenic mice chow a normal fat diet exhibited vascular abnormalities resembling atherosclerosis.
IL-32 acts as a proinflammatory factor and may be implicated in the inflammatory cascade contributing to atherosclerosis. By promoting the synthesis of matrix metalloproteinases, it may further contribute to plaque instability. Further studies are warranted to investigate whether IL-32 may serve as a potential therapeutic target in fighting atherosclerosis.
IL-32 先前已被证实可促进类风湿关节炎患者的炎症反应，并有助于人脐静脉内皮细胞（HUVEC）中 IL-1β 诱导的 ICAM-1 以及其他促炎细胞因子的合成。鉴于 RA 患者中动脉粥样硬化的发生率较高，这些观察结果表明 IL-32 可能参与动脉粥样硬化的炎症途径。
通过定量实时 PCR 和免疫组织化学检测人动脉粥样硬化血管壁组织中 IL-32 的 mRNA 和蛋白水平。用促炎细胞因子和 TLR 配体刺激 HUVEC 和 M1/M2 巨噬细胞，以评估 IL-32 mRNA 的诱导。用 AdIL-32γ 转导人 THP1 巨噬细胞，以研究几种促动脉粥样硬化介质的诱导。最后，研究了 IL-32γ 转基因小鼠的主动脉，并与年龄匹配的野生型小鼠的主动脉进行了比较。
IL-32 在人动脉粥样硬化血管壁中可检测到表达，IL-32β 和 IL-32γ mRNA 的表达显著增强。TLR3 配体 Poly I:C 与 IFNγ 联合作用于 HUVEC 和 M1/M2 巨噬细胞时，对 IL-32 mRNA 的诱导作用最强。人 THP1 巨噬细胞中 IL-32γ 的腺病毒过表达导致 CCL2、sVCAM-1、MMP1、MMP9 和 MMP13 的产生增加。IL-32γ 转基因小鼠在正常脂肪饮食下表现出类似于动脉粥样硬化的血管异常。
IL-32 作为一种促炎因子，可能与促进动脉粥样硬化的炎症级联反应有关。通过促进基质金属蛋白酶的合成，它可能进一步导致斑块不稳定。需要进一步的研究来探讨 IL-32 是否可作为治疗动脉粥样硬化的潜在靶点。
