Morehouse School of Medicine, Atlanta, Georgia, USA.
Emory University School of Medicine, Atlanta, Georgia, USA.
Cannabis Cannabinoid Res. 2023 Jun;8(3):434-444. doi: 10.1089/can.2022.0277. Epub 2023 Apr 19.
The endogenous cannabinoid (endocannabinoid) system is an emerging target for the treatment of chronic inflammatory disease with the potential to advance treatment for many respiratory illnesses. The varied effects of endocannabinoids across tissue types makes it imperative that we explore their physiologic impact within unique tissue targets. The aim of this scoping review is to explore the impact of endocannabinoid activity on eicosanoid production as a measure of human airway inflammation. A scoping literature review was conducted according to PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Search strategies using MeSH terms related to cannabinoids, eicosanoids, cyclooxygenase (COX), and the respiratory system were used to query Medline, Embase, Cochrane, CINAHL, Web of Science, and Biosis Previews in December 2021. Only studies that investigated the relationship between endocannabinoids and the eicosanoid system in mammalian respiratory tissue after 1992 were included. Sixteen studies were incorporated in the final qualitative review. Endocannabinoid activation increases COX-2 expression, potentially through ceramide-dependent or p38 and p42/44 Mitogen-Activated Protein Kinase pathways and is associated with a concentration-dependent increase in prostaglandin (PG)E. Inhibitors of endocannabinoid hydrolysis found either an increase or no change in levels of PGE and PGD and decreased levels of leukotriene (LT)B, PGI, and thromboxane A (TXA). Endocannabinoids increase bronchial epithelial cell permeability and have vasorelaxant effects in human pulmonary arteries and cause contraction of bronchi and decreased gas trapping in guinea pigs. Inhibitors of endocannabinoid hydrolysis were found to have anti-inflammatory effects on pulmonary tissue and are primarily mediated by COX-2 and activation of eicosanoid receptors. Direct agonism of endocannabinoid receptors appears to play a minor role. The endocannabinoid system has diverse effects on the mammalian airway. While endocannabinoid-derived PGs can have anti-inflammatory effects, endocannabinoids also produce proinflammatory conditions, such as increased epithelial permeability and bronchial contraction. These conflicting findings suggest that endocannabinoids produce a variety of effects depending on their local metabolism and receptor agonism. Elucidation of the complex interplay between the endocannabinoid and eicosanoid pathways is key to leveraging the endocannabinoid system as a potential therapeutic target for human airway disease.
内源性大麻素（内源性大麻素）系统是治疗慢性炎症性疾病的新兴靶点，有可能推进许多呼吸系统疾病的治疗。内源性大麻素在不同组织类型中的多种作用使得我们必须探索它们在独特的组织靶标中的生理影响。本范围综述的目的是探讨内源性大麻素活性对花生四烯酸产物（作为人类气道炎症的衡量标准）的影响。
根据 PRISMA-ScR（系统评价和荟萃分析扩展的首选报告项目用于范围综述）指南进行了范围文献综述。使用与大麻素、花生四烯酸、环氧化酶 (COX) 和呼吸系统相关的 MeSH 术语的搜索策略，于 2021 年 12 月查询了 Medline、Embase、Cochrane、CINAHL、Web of Science 和 Biosis Previews。仅纳入了 1992 年后研究哺乳动物呼吸组织中内源性大麻素与花生四烯酸系统之间关系的研究。
最终纳入了 16 项定性综述研究。内源性大麻素的激活增加了 COX-2 的表达，可能通过神经酰胺依赖性或 p38 和 p42/44 丝裂原激活蛋白激酶途径，并且与前列腺素 (PG)E 浓度依赖性增加相关。内源性大麻素水解抑制剂发现 PGE 和 PGD 的水平增加或不变，而白三烯 (LT)B、PGI 和血栓烷 A (TXA) 的水平降低。内源性大麻素增加支气管上皮细胞通透性，并在人体肺动脉中具有血管舒张作用，导致豚鼠支气管收缩和气体捕获减少。内源性大麻素水解抑制剂被发现对肺组织具有抗炎作用，主要通过 COX-2 和激活花生四烯酸受体介导。内源性大麻素受体的直接激动似乎作用较小。
内源性大麻素系统对哺乳动物气道有多种影响。虽然内源性大麻素衍生的 PG 可以具有抗炎作用，但内源性大麻素也会产生促炎状态，例如上皮通透性增加和支气管收缩。这些相互矛盾的发现表明，内源性大麻素根据其局部代谢和受体激动剂产生多种作用。阐明内源性大麻素和花生四烯酸途径之间的复杂相互作用对于利用内源性大麻素系统作为人类气道疾病的潜在治疗靶点至关重要。
