Fiorucci G, Percario Z A, Coccia E M, Battistini A, Rossi G B, Romeo G, Affabris E
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
J Interferon Cytokine Res. 1995 May;15(5):395-402. doi: 10.1089/jir.1995.15.395.
Hemin and other metalloporphyrins are known as very versatile compounds in nature, because they are able to carry out numerous functions in a free state or in association with specific proteins. When Friend murine erythroleukemia cells are treated with IFN-beta plus 100 microM hemin, the antiviral state is not observed, whereas the antiviral effect of IFN-gamma is unaffected by hemin treatment. This inhibitory effect of hemin is not restricted to erythroid cells. In fact, it is also observed in murine L929 and in human cell lines treated with IFN-beta. Neither trivalent iron in other forms nor hemin analogs (such as protoporphyrin IX or Sn(2+)-protoporphyrine IX) mimic this effect. Conversely, Co(3+)-protoporphyrin IX was as effective as hemin. At the transcriptional level, results obtained by run-on assays on nuclei from IFN-treated cells indicate that hemin does not completely inhibit IFN-beta induction of 2-5A synthetase gene(s) at 6 h of treatment but abolishes it at 24 h. In addition, hemin is able to inhibit the accumulation of IFN-induced 2-5A synthetase mRNAs. Experiments carried out to investigate the hemin effect on the early steps of the IFN signaling pathway indicate that hemin interferes with the ability of type I IFN to bind to its receptor, probably by a direct action on the IFN molecule.
血红素和其他金属卟啉在自然界中是非常通用的化合物，因为它们能够以游离状态或与特定蛋白质结合的形式发挥多种功能。当用干扰素-β（IFN-β）加100微摩尔血红素处理弗氏小鼠红白血病细胞时，未观察到抗病毒状态，而干扰素-γ（IFN-γ）的抗病毒作用不受血红素处理的影响。血红素的这种抑制作用并不局限于红细胞。事实上，在用IFN-β处理的小鼠L929细胞和人细胞系中也观察到了这种作用。其他形式的三价铁和血红素类似物（如原卟啉IX或锡（2+）-原卟啉IX）均未模拟这种作用。相反，钴（3+）-原卟啉IX与血红素的效果相同。在转录水平上，通过对IFN处理细胞的细胞核进行连续分析获得的结果表明，血红素在处理6小时时并未完全抑制IFN-β诱导的2-5A合成酶基因，但在24小时时则消除了这种诱导作用。此外，血红素能够抑制IFN诱导的2-5A合成酶mRNA的积累。为研究血红素对IFN信号通路早期步骤的影响而进行的实验表明，血红素可能通过对IFN分子的直接作用来干扰I型IFN与其受体结合的能力。
