Department of Medicine, Hem-Onc Section, OU Cancer Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Curr Mol Med. 2009 Jun;9(5):565-79. doi: 10.2174/156652409788488748.
Recently, lipoxins (LXs) and resolvins (Rvs) have become the topic of intense interest because of expanding views of their action, particularly in chronic disorders where unresolved inflammation is a key factor leading to colon carcinogenesis. Rvs are biosynthesized from omega-3 fatty acids eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) via cyclooxygenase-2/lipoxygenase (COX-2/LOX) pathways; Rvs are shown to dramatically reduce dermal inflammation, peritonitis, dendritic cell migration, and interleukin production. This explains that dietary supplementation of omega-3 fatty acids generates potent local endogenous mediators that control inflammation. LXs are biosynthesized from COX-2/LOX pathways. Metabolites of 15-LOX-1 and 2 are anti-tumorigenic; similarly, 15-epi-LXA(4) synthesized during COX-2 acetylation by low doses of aspirin too possesses anti-tumorigenic effects. Acetylating nonsteroidal anti-inflammatory drugs (NSAIDs), like aspirin, switches COX-2 from forming PGE(2) (promoting tumorigenesis) to 15-epi-LXA(4) (antitumorigenesis). LXs and Rvs are endogenously generated during the spontaneous resolution phase. These newly identified LXs and Rvs have proved to be potent regulators of both leukocytes and cytokine productions, thereby regulating the events of interest in inflammation and resolution. In light of existing knowledge on interconnected pathways of pro-inflammatory mediators (leukotrienes, chemokines (IL8, SDF-1 alpha, MIP-1 alpha, MCP-1,2 etc), and cytokines (IL3, IL6, IL12, IL-1 beta, GM-CSF, B94, TNF-alpha etc)), the anti-inflammatory properties of pro-resolving mediators in preventing chronic inflammation which leads to carcinogenesis needs further understanding. In this review, we explore the mechanisms that trigger formation of LXs and Rvs, to highlight the relative importance of LXs and Rvs in carcinogenesis in relation to pro-inflammatory mediators.
最近，内脂素（LXs）和消退素（Rvs）由于其作用的观点不断扩大而成为研究热点，特别是在慢性疾病中，未解决的炎症是导致结肠癌发生的关键因素。Rvs 是由ω-3 脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）通过环加氧酶-2/脂加氧酶（COX-2/LOX）途径生物合成的；Rvs 可显著减少皮肤炎症、腹膜炎、树突状细胞迁移和白细胞介素的产生。这表明膳食补充ω-3 脂肪酸会产生有效的局部内源性介质来控制炎症。LXs 是由 COX-2/LOX 途径生物合成的。15-LOX-1 和 2 的代谢产物具有抗肿瘤作用；同样，低剂量阿司匹林乙酰化时由 COX-2 合成的 15-epi-LXA(4)也具有抗肿瘤作用。乙酰化非甾体抗炎药（如阿司匹林）会使 COX-2 从形成 PGE(2)（促进肿瘤发生）转变为 15-epi-LXA(4)（抗肿瘤发生）。LXs 和 Rvs 是在自发消退阶段内源性生成的。这些新发现的 LXs 和 Rvs 已被证明是白细胞和细胞因子产生的有效调节剂，从而调节炎症和消退过程中的相关事件。鉴于促炎介质（白三烯、趋化因子（IL8、SDF-1 alpha、MIP-1 alpha、MCP-1、2 等）和细胞因子（IL3、IL6、IL12、IL-1 beta、GM-CSF、B94、TNF-alpha 等）的相互关联途径的现有知识，需要进一步了解预防导致癌变的慢性炎症的促消退介质的抗炎特性。在这篇综述中，我们探讨了触发 LXs 和 Rvs 形成的机制，以强调 LXs 和 Rvs 在与促炎介质相关的致癌作用中的相对重要性。
