Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and was initially described as an IFN-γ-inducing factor derived from anti-CD3-stimulated T-helper (Th)1 cells. IL-18 plays a significant role in the activation of hematopoietic cell types mediating both Th1 and Th2 responses and is the primary inducer of interferon-γ in these cells. The biological activity of IL-18 is mediated through its binding to the IL-18 receptor complex and activation of nuclear factor-κB (NF-κB), culminating in the production and release of several cytokines, chemokines, and cellular adhesion molecules. In certain cell types, IL-18 also activates mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase/ AKT serine/threonine kinase (PI3K/AKT) signaling modules leading to the production and release of proinflammatory cytokines. IL-18-mediated signaling acts as one of the vital components of the immunomodulatory cytokine networks involved in host defense, inflammation, and tissue regeneration. Albeit its biomedical importance, a comprehensive resource of IL-18 mediated signaling pathway is currently lacking. In this study, we report on the development of an integrated pathway map of IL-18/IL-18R signaling. The pathway map was developed through literature mining from published literature based on manual curation guidelines adapted from NetPath and includes information on 16 protein-protein interaction events, 38 enzyme-catalysis events, 12 protein translocation events, 26 activations/inhibition events, transcriptional regulators, 230 gene regulation events and 84 induced protein expression events. The IL-18 signaling pathway can be freely accessed through the WikiPathways database (https://www.wikipathways.org/index.php/Pathway:WP4754).

中文翻译：

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IL-18 介导的信号传导的综合通路图。

白细胞介素 18 (IL-18) 是 IL-1 细胞因子家族的成员，最初被描述为源自抗 CD3 刺激的 T 辅助 (Th)1 细胞的 IFN-γ 诱导因子。IL-18 在介导 Th1 和 Th2 反应的造血细胞类型的激活中起重要作用，并且是这些细胞中干扰素-γ 的主要诱导剂。IL-18 的生物活性是通过其与 IL-18 受体复合物的结合和核因子-κB (NF-κB) 的激活来介导的，最终导致产生和释放多种细胞因子、趋化因子和细胞粘附分子。在某些细胞类型中，IL-18 还激活丝裂原活化蛋白激酶 (MAPK) 和磷酸肌醇 3-激酶/AKT 丝氨酸/苏氨酸激酶 (PI3K/AKT) 信号模块，导致促炎细胞因子的产生和释放。IL-18 介导的信号传导是参与宿主防御、炎症和组织再生的免疫调节细胞因子网络的重要组成部分之一。尽管具有生物医学重要性，但目前缺乏 IL-18 介导的信号通路的综合资源。在这项研究中，我们报告了 IL-18/IL-18R 信号通路整合通路图的开发。路径图是根据 NetPath 改编的手动管理指南，通过对已发表文献的文献挖掘开发的，包括有关 16 个蛋白质-蛋白质相互作用事件、38 个酶催化事件、12 个蛋白质易位事件、26 个激活/抑制事件、转录调节因子的信息， 230 个基因调控事件和 84 个诱导蛋白表达事件。