Laboratory of Immunopathology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, MG, Brazil.
Vet Res. 2013 Oct 2;44(1):89. doi: 10.1186/1297-9716-44-89.
Heme oxygenase-1 (HO-1) is an enzyme that catabolizes free heme, which induces an intense inflammatory response. The expression of HO-1 is induced by different stimuli, triggering an anti-inflammatory response during biological stress. It was previously verified that HO-1 is able to induce indoleamine 2,3-dioxygenase (IDO), an enzyme that is induced by IFN-γ in Toxoplasma gondii infection. To verify the role of HO-1 during in vivo T. gondii infection, BALB/c and C57BL/6 mice were infected with the ME49 strain and treated with zinc protoporphyrin IX (ZnPPIX) or hemin, which inhibit or induce HO-1 activity, respectively. The results show that T. gondii infection induced high levels of HO-1 expression in the lung of BALB/c and C57BL6 mice. The animals treated with ZnPPIX presented higher parasitism in the lungs of both lineages of mice, whereas hemin treatment decreased the parasite replication in this organ and in the small intestine of infected C57BL/6 mice. Furthermore, C57BL/6 mice infected with T. gondii and treated with hemin showed higher levels of IDO expression in the lungs and small intestine than uninfected mice. In conclusion, our data suggest that HO-1 activity is involved in the control of T. gondii in the lungs of both mouse lineages, whereas the hemin, a HO-1 inducer, seems to be involved in the control of parasitism in the small intestine of C57BL/6 mice.
血红素加氧酶-1(HO-1)是一种分解游离血红素的酶,它会引起强烈的炎症反应。HO-1 的表达受多种刺激诱导,在生物应激时引发抗炎反应。先前已经证实,HO-1 能够诱导吲哚胺 2,3-双加氧酶(IDO),后者在弓形虫感染中受 IFN-γ诱导。为了验证 HO-1 在体内弓形虫感染中的作用,用 ME49 株感染 BALB/c 和 C57BL/6 小鼠,并分别用锌原卟啉 IX(ZnPPIX)或血红素处理,前者抑制 HO-1 活性,后者诱导其活性。结果表明,弓形虫感染诱导 BALB/c 和 C57BL6 小鼠肺部 HO-1 表达水平升高。用 ZnPPIX 处理的动物在两种小鼠品系的肺部寄生率更高,而血红素处理则降低了该器官和感染 C57BL/6 小鼠小肠中的寄生虫复制。此外,感染弓形虫并用血红素处理的 C57BL/6 小鼠肺部和小肠中的 IDO 表达水平高于未感染的小鼠。总之,我们的数据表明,HO-1 活性参与了两种小鼠品系肺部弓形虫的控制,而血红素(HO-1 诱导剂)似乎参与了 C57BL/6 小鼠小肠寄生虫的控制。