El Mezayen Rabab, El Gazzar Mohamed, Nicolls Mark R, Marecki John C, Dreskin Stephen C, Nomiyama Hisayuki
Department of Medicine, University of Colorado, Health Sciences Center, Denver, 80262, USA.
Immunol Lett. 2006 Jul 15;106(1):72-81. doi: 10.1016/j.imlet.2006.04.012. Epub 2006 May 22.
Prostaglandins (PGs) are potent proinflammatory mediators generated through arachidonic acid metabolism by cyclooxygenase-1 and -2 (COX-1 and COX-2) in response to different stimuli and play an important role in modulating the inflammatory responses in a number of conditions, including allergic airway inflammation. Thymoquinone (TQ) is the main active constituent of the volatile oil extract of Nigella sativa seeds and has been reported to have anti-inflammatory properties. We examined the effect of TQ on the in vivo production of PGs and lung inflammation in a mouse model of allergic airway inflammation. Mice sensitized and challenged through the airways with ovalbumin (OVA) exhibited a significant increase in PGD2 and PGE2 production in the airways. The inflammatory response was characterized by an increase in the inflammatory cell numbers and Th2 cytokine levels in the bronchoalveolar lavage (BAL) fluid, lung airway eosinophilia and goblet cell hyperplasia, as well as the induction of COX-2 protein expression in the lung. Intraperitoneal injection of TQ for 5 days before the first OVA challenge attenuated airway inflammation as demonstrated by the significant decrease in Th2 cytokines, lung eosinophilia, and goblet cell hyperplasia. This attenuation of airway inflammation was concomitant to the inhibition of COX-2 protein expression and PGD2 production. However, TQ had a slight inhibitory effect on COX-1 expression and PGE2 production. These findings suggest that TQ has an anti-inflammatory effect during the allergic response in the lung through the inhibition of PGD2 synthesis and Th2-driven immune response.
前列腺素（PGs）是一类强效的促炎介质，由环氧合酶-1和-2（COX-1和COX-2）通过花生四烯酸代谢产生，以响应不同刺激，并在多种情况下调节炎症反应中发挥重要作用，包括过敏性气道炎症。百里醌（TQ）是黑种草籽挥发油提取物的主要活性成分，据报道具有抗炎特性。我们在过敏性气道炎症小鼠模型中研究了TQ对PGs体内产生和肺部炎症的影响。通过气道用卵清蛋白（OVA）致敏和激发的小鼠气道中PGD2和PGE2的产生显著增加。炎症反应的特征是支气管肺泡灌洗（BAL）液中炎症细胞数量和Th2细胞因子水平增加、肺气道嗜酸性粒细胞增多和杯状细胞增生，以及肺中COX-2蛋白表达的诱导。在首次OVA激发前5天腹腔注射TQ可减轻气道炎症，表现为Th2细胞因子、肺嗜酸性粒细胞增多和杯状细胞增生显著减少。气道炎症的这种减轻与COX-2蛋白表达和PGD2产生的抑制同时发生。然而，TQ对COX-1表达和PGE2产生有轻微抑制作用。这些发现表明，TQ通过抑制PGD2合成和Th2驱动的免疫反应在肺部过敏反应期间具有抗炎作用。
