Willis D, Moore A R, Frederick R, Willoughby D A
Department of Experimental Pathology, William Harvey Research Institute, St Bartholomew's Hospital Medical College, London, UK.
Nat Med. 1996 Jan;2(1):87-90. doi: 10.1038/nm0196-87.
Chronic inflammatory diseases place a heavy social and economic burden on the resources of many nations, but the number of safe and effective treatments is limited. To date, the major research effort has concentrated on those mediators responsible for the initiation and maintenance of the pathological process. In contrast, little attention has been focused on endogenous factors responsible for the resolution of the inflammation. Heme oxygenase ((HO); EC 1.14.99.3) is the rate-limiting enzyme in the catabolism of heme to biliverdin (which is converted to bilirubin by biliverdin reductase), free iron and carbon monoxide (CO). Two isoforms of HO have been characterized, the constitutive isoform, HO-2, which is the major isoform present under physiological conditions, and the stress-induced isoform, HO-1, which has also been classified as heat-shock protein 32K (ref. 1). Increases in HO activity have been implicated in tissue protection against oxidative stress. In this communication, we describe the effects of modulating HO during an acute complement-dependent inflammatory response. Elevation of this enzyme resulted in a striking suppression, whereas inhibition of the enzyme led to a potentiation of the inflammatory response. Such novel enzyme modulation has application on the one hand to the treatment of inflammatory diseases and on the other hand to immnosuppressed states in which the impaired ability to mount an adequate inflammatory response may result in death from opportunistic infections.
慢性炎症性疾病给许多国家的资源带来了沉重的社会和经济负担，但安全有效的治疗方法数量有限。迄今为止，主要的研究工作集中在那些负责启动和维持病理过程的介质上。相比之下，对负责炎症消退的内源性因素关注较少。血红素加氧酶（（HO）；EC 1.14.99.3）是血红素分解代谢为胆绿素（由胆绿素还原酶转化为胆红素）、游离铁和一氧化碳（CO）的限速酶。已鉴定出HO的两种同工型，即组成型同工型HO-2，它是生理条件下存在的主要同工型，以及应激诱导型同工型HO-1，它也被归类为热休克蛋白32K（参考文献1）。HO活性的增加与组织对氧化应激的保护作用有关。在本通讯中，我们描述了在急性补体依赖性炎症反应期间调节HO的作用。该酶的升高导致显著的抑制作用，而该酶的抑制则导致炎症反应的增强。这种新型的酶调节一方面可应用于炎症性疾病的治疗，另一方面可应用于免疫抑制状态，在这种状态下，引发充分炎症反应的能力受损可能导致因机会性感染而死亡。
