The Wnt pathway: A macrophage effector molecule that triggers inflammation
The Wnt pathway: A macrophage effector molecule that triggers inflammation
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DOI：
10.1007/s11883-009-0036-4
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发表时间：
2009-05-01
影响因子：
5.8
通讯作者：
Schoedon, Gabriele
中科院分区：
文献类型：
--
作者：
Pereira, Claudia P.;Bachli, Esther B.;Schoedon, Gabriele
Wnt蛋白是负责细胞分化和发育以及肿瘤和退行性过程的高度保守的无翅蛋白家族的成员。最近，Toll样受体介导的Wnt信号被发现与果蝇的先天免疫有关。在微生物挑战后，人巨噬细胞中Wnt5A的上调表明了类似的机制。Toll样受体介导的Wnt5A表达是通过自分泌和旁分泌信号传导持续炎症巨噬细胞活化的关键过程。通过活化的蛋白C下调Wnt5A表达和随后的炎性巨噬细胞应答的减弱支持炎症和凝血（另一种高度保守的生物系统）之间的联系。脓毒症患者中Wnt5A水平高于健康个体的发现提供了Wnt5A与严重全身性炎症相关的直接证据。Wnt5A信号传导可以通过抗炎介质调节的事实使得这种效应分子成为炎性疾病中治疗干预的有吸引力的靶标。
Wnt proteins are members of the highly conserved wingless family of proteins responsible for cell differentiation and development and for neoplastic and degenerative processes. Recently, Toll-like receptor-mediated Wnt signaling was found to be associated with innate immunity in Drosophila. Upregulation of Wnt5A in human macrophages upon microbial challenge indicated a similar mechanism. Toll-like receptor-mediated Wnt5A expression is a key process for sustained inflammatory macrophage activation through autocrine and paracrine signaling. Downregulation of Wnt5A expression and subsequent attenuation of inflammatory macrophage responses by activated protein C supports the link between inflammation and coagulation, another highly conserved biologic system. Direct evidence for the relevance of Wnt5A in severe systemic inflammation is provided by the finding of higher Wnt5A levels in patients with sepsis than in healthy individuals. The fact that Wnt5A signaling can be modulated by anti-inflammatory mediators makes this effector molecule an attractive target for therapeutic intervention in inflammatory diseases.