Department of Pharmacology, Faculty of Medicine, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, NS, B3H 4R2, Canada.
Inflamm Res. 2021 May;70(5):525-538. doi: 10.1007/s00011-021-01454-1. Epub 2021 Mar 15.
As an integral part of the innate immune system, the epithelial membrane is exposed to an array of insults that may trigger an immune response. One of the immune system's main functions is to regulate the level of communications between the mucosa and the lumen of various tissues. While it is clear that inhaled or ingested substances, or microorganisms may induce changes that affect the epithelial barrier in various ways, the proteins involved in the signaling cascades and physiological events leading to the regulation and maintenance of the barrier are not always well characterized. We review here some of the signaling components involved in regulating the barrier's paracellular permeability, and their potential effects on the activation of an immune response. While an effective immune response must be launched against pathogenic insults, tolerance must also be maintained for non-pathogenic antigens such as those in the commensal flora or for endogenous metabolites. Along with other members of the innate and adaptive immunity, the endocannabinoid system also plays an instrumental role in maintaining the balance between inflammation and tolerance. We discuss the potential effects of endo- and phytocannabinoids on epithelial permeability and how the dysregulation of this system could be involved in diseases and targeted for therapy.
作为先天免疫系统的一个组成部分，上皮膜暴露于一系列可能引发免疫反应的刺激物中。免疫系统的主要功能之一是调节各种组织的黏膜和腔之间的通讯水平。虽然很明显，吸入或摄入的物质或微生物可能会以各种方式诱导影响上皮屏障的变化，但参与信号级联和导致屏障调节和维持的生理事件的蛋白质并不总是很好地描述。我们在这里回顾了一些参与调节屏障旁通透性的信号成分，以及它们对激活免疫反应的潜在影响。虽然必须对致病刺激物发起有效的免疫反应，但也必须对非致病抗原（如共生菌群中的抗原或内源性代谢物）保持耐受。与先天和适应性免疫的其他成员一样，内源性大麻素系统也在维持炎症和耐受之间的平衡方面发挥着重要作用。我们讨论了内源性和植物源大麻素对上皮通透性的潜在影响，以及该系统的失调如何可能与疾病有关，并成为治疗的靶点。
