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Role of IL-18 in transplant biology.
European Cytokine Network ( IF 2.8 ) Pub Date : 2018-08-30 , DOI: 10.1684/ecn.2018.0410
Chen Liu 1 , Juntao Chen 1 , Baoqing Liu 1 , Shunzong Yuan 2 , Dawei Shou 3 , Liang Wen 1 , Xiaoying Wu 4 , Weihua Gong 1
Affiliation  

Since pro-inflammatory cytokine IL-18 and its receptor (IL-18R) are closely involved in regulating both adaptive and innate immune responses, it is conceivable that they might play an important role in organ transplantation. IL-18 can stimulate lymphocytes to produce the IFN-γ and regulate macrophage activity, thereby increasing the expression of proinflammatory cytokines including IL-1β, IL-6, CCL4 (macrophage inflammatory protein-1β), CXCL2 (macrophage inflammatory protein-2), and CCL2 (monocyte chemotactic protein-1). Nevertheless, the IL-18 signaling pathway and its underlying mechanisms remain obscure in transplant biology. This review is to summarize recent advances in our knowledge about the IL-18 signaling pathway and to analyze their functions in transplant-related biology. It was found that IL-18/IL-18R signaling pathway contributed to vascular transplantation, ischemmia/reperfusion, acute kidney injury, and acute rejection of kidney/liver/heart transplantation. IL-18 was a potential CYP3A expression modulator and was capable of affecting tacrolimus pharmacokinetics. Neutralizing IL-18 by its inhibitor IL-18 binding protein could efficiently suppress the production of injury-associated cytokines such as IL-6, TNF-α, IFN-γ, CXCL10 (IFN-γ-inducible protein10), and CX3CL1 (fractalkine) and improve allograft function. Blockade of IL-18 signaling could regulate cardiomyocyte apoptosis and inhibit Th17 cells differentiation. Alteration of IL-18 levels was suggested as a biomarker for predicting ongoing allograft outcome. All these activities could deepen our understanding of immunobiological role of IL-18 and its receptor in the field of organ transplantation. Intervention of IL-18 signaling pathway might be utilized as a therapeutic strategy in clinic.

中文翻译:

IL-18在移植生物学中的作用。

由于促炎性细胞因子IL-18及其受体(IL-18R)与调节适应性免疫反应和先天性免疫反应密切相关,因此可以想象它们可能在器官移植中起重要作用。IL-18可刺激淋巴细胞产生IFN-γ并调节巨噬细胞活性,从而增加促炎细胞因子的表达,包括IL-1β,IL-6,CCL4(巨噬细胞炎性蛋白-1β),CXCL2(巨噬细胞炎性蛋白-2)。和CCL2(单核细胞趋化蛋白1)。然而,IL-18信号传导途径及其潜在机制在移植生物学中仍然不清楚。这篇综述旨在总结我们对IL-18信号传导途径的认识的最新进展,并分析其在移植相关生物学中的功能。发现IL-18 / IL-18R信号传导途径有助于血管移植,局部缺血/再灌注,急性肾损伤和肾/肝/心脏移植的急性排斥反应。IL-18是潜在的CYP3A表达调节剂,能够影响他克莫司的药代动力学。通过其抑制剂IL-18结合蛋白中和IL-18可有效抑制损伤相关细胞因子的产生,例如IL-6,TNF-α,IFN-γ,CXCL10(IFN-γ诱导蛋白10)和CX3 CL1(fractalkine)并改善同种异体移植功能。IL-18信号传导的阻滞可以调节心肌细胞凋亡并抑制Th17细胞分化。IL-18水平的改变被认为是预测正在进行的同种异体移植结果的生物标记。所有这些活动可以加深我们对IL-18及其受体在器官移植领域的免疫生物学作用的了解。IL-18信号通路的干预可作为临床治疗策略。
更新日期:2018-08-30
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