Marcinkiewicz Janusz, Walczewska Maria, Olszanecki Rafał, Bobek Małgorzata, Biedroń Rafał, Dulak Józef, Józkowicz Alicja, Kontny Ewa, Maślinski Włodzimierz
Chair of Immunology, Institute of Rheumatology, Poland.
Adv Exp Med Biol. 2009;643:439-50. doi: 10.1007/978-0-387-75681-3_46.
Taurine chloramine (TauCl) and Taurine bromamine (TauBr), products of the neutrophil myeloperoxidase halide system, exert anti-inflammatory properties. They inhibit the production of a variety of inflammatory mediators, such as prostaglandin E2 (PGE2), nitric oxide (NO) and proinflammatory cytokines. Heme oxygenase-1 (HO-1), a stress inducible enzyme, degrades heme to biliverdin, free iron and carbon monoxide (CO), which are involved in the anti-inflammatory and antioxidant actions of HO-1. Recently we have demonstrated that taurine haloamines induce the expression of HO-1 in inflammatory cells. In this study we examined whether HO-1 participates in taurine haloamines-mediated suppression of proinflammatory cytokine production. We have shown that TauCl/TauBr and CO inhibit the production of TNF-alpha, IL-12 and IL-6, in a similar dose-dependent manner. However, the suppressor activity of TauCl was not altered in HO-1 deficient mice. Therefore, HO-1 and TauCl may independently regulate the production of proinflammatory cytokines. We suggest that TauCl and TauBr provide a link between the two antioxidant systems: the cysteine pathway and the heme oxygenase system.
牛磺酸氯胺(TauCl)和牛磺酸溴胺(TauBr)是中性粒细胞髓过氧化物酶卤化物系统的产物,具有抗炎特性。它们可抑制多种炎症介质的产生,如前列腺素E2(PGE2)、一氧化氮(NO)和促炎细胞因子。血红素加氧酶-1(HO-1)是一种应激诱导酶,可将血红素降解为胆绿素、游离铁和一氧化碳(CO),这些物质参与了HO-1的抗炎和抗氧化作用。最近我们证明,牛磺酸卤胺可诱导炎症细胞中HO-1的表达。在本研究中,我们检测了HO-1是否参与牛磺酸卤胺介导的促炎细胞因子产生的抑制作用。我们发现,TauCl/TauBr和CO以相似的剂量依赖性方式抑制肿瘤坏死因子-α(TNF-α)、白细胞介素-12(IL-12)和白细胞介素-6(IL-6)的产生。然而,在HO-1缺陷小鼠中,TauCl的抑制活性并未改变。因此,HO-1和TauCl可能独立调节促炎细胞因子的产生。我们认为,TauCl和TauBr在两个抗氧化系统之间建立了联系:半胱氨酸途径和血红素加氧酶系统。