Nowak Jerzy Z
Zakład Farmakologii, Katedra Farmakologii i Farmakologii Klinicznej Uniwersytetu Medycznego w Łodzi.
Postepy Hig Med Dosw (Online). 2010 Mar 17;64:115-32.
Inflammation is a physiological defense reaction of living tissues to injury or infection. An array of mediators, including those derived from omega-6 (omega6) polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA) e.g. prostaglandins and leukotrienes, promote the inflammatory response. Acute inflammation has several programmed fates, including complete resolution or progression to chronic inflammation, scarring, and eventual loss of tissue function. Studies on AA-derived proinflammatory mediators led to the discovery of AA-derived anti-inflammatory and pro-resolving compounds. These include lipoxins, originating from AA, and resolvins, originating from the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as well as the omega-6 PUFA docosapentaenoic acid (DPA-omega6). DHA is also a substrate for other anti-inflammatory mediators, i.e. neuroprotectin and maresin. Because of their role in the final phase of acute inflammation, i.e. the resolution of inflammation, the above anti-inflammatory mediators were named pro-resolving mediators. They are formed in cooperating cells present in the region of inflammation in a process called transcellular biosynthesis with the aid of specific lipoxygenases (LOX) and cyclooxygenases (COX). Pro-resolving anti-inflammatory mediators exert their biological activities in a receptor-dependent manner in the resolution phase of inflammation. Of their various biological effects, the most important include inhibition of leukocyte mobilization and traffic through endothelial or epithelial layers, suppression of proinflammatory cytokine release by different cells present in inflamed tissue, and stimulation of the phagocytic activity of monocytes/macrophages. This article surveys the current knowledge on inflammation and the role of the pro-resolving and anti-inflammatory potential of lipid-derived agonistic mediators.
炎症是活组织对损伤或感染的一种生理防御反应。一系列介质,包括那些源自ω-6(ω6)多不饱和脂肪酸(PUFA)的介质,如花生四烯酸(AA),例如前列腺素和白三烯,可促进炎症反应。急性炎症有几种既定的转归,包括完全消退或进展为慢性炎症、瘢痕形成以及最终组织功能丧失。对源自AA的促炎介质的研究导致发现了源自AA的抗炎和促消退化合物。这些包括源自AA的脂氧素,以及源自ω-3多不饱和脂肪酸二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)以及ω-6多不饱和脂肪酸二十二碳五烯酸(DPA-ω6)的消退素。DHA也是其他抗炎介质即神经保护素和促消退素的底物。由于它们在急性炎症的最后阶段即炎症消退中所起的作用,上述抗炎介质被称为促消退介质。它们在炎症区域存在的协同细胞中通过特定脂氧合酶(LOX)和环氧化酶(COX)的辅助,在一个称为跨细胞生物合成的过程中形成。促消退抗炎介质在炎症消退阶段以受体依赖性方式发挥其生物学活性。在它们的各种生物学效应中,最重要的包括抑制白细胞通过内皮或上皮层的动员和运输,抑制炎症组织中不同细胞释放促炎细胞因子以及刺激单核细胞/巨噬细胞的吞噬活性。本文综述了关于炎症以及脂质衍生激动介质的促消退和抗炎潜力作用的当前知识。