Dusi S, Donini M, Lissandrini D, Mazzi P, Bianca V D, Rossi F
Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy.
Eur J Immunol. 2001 Mar;31(3):929-38. doi: 10.1002/1521-4141(200103)31:3<929::aid-immu929>3.0.co;2-m.
Human blood monocytes lose their capability to produce microbicidal oxidants during culture. We report that this process is associated with decreased gp91phox, p22phox and p47phox expression, release of PU.1 and CP-1 from gp91phox promoter, and PU.1 from p47phox promoter. However, in presence of IFN-gamma or TNF-alpha, the superoxide anion (O(2)(-)) production, the p47phox, gp91phox and p22phox expression, and the binding of PU.1 and CP-1 to DNA are maintained at the high levels observed in blood monocytes. To clarify the role of PU.1 in the expression of NADPH oxidase components, oligonucleotides competing for PU.1-DNA binding were added to cultured monocytes. These oligonucleotides abrogated the maintenance of gp91phox and p22phox expression by IFN-gamma and TNF-alpha, but did not inhibit the effect of these cytokines on p47phox expression and O(2)(-) production. Our results indicate that in monocytes the IFN-gamma- and TNF-alpha-induced expression of gp91phox and p22phox, but not p47phox, requires the binding of PU.1 to gp91phox promoter. However, the preservation of O(2)(-) production by IFN-gamma and TNF-alpha is unrelated to their effect on gp91phox and p22phox expression.
人血单核细胞在培养过程中失去产生杀菌性氧化剂的能力。我们报告，这一过程与gp91phox、p22phox和p47phox表达降低、PU.1和CP-1从gp91phox启动子释放以及PU.1从p47phox启动子释放有关。然而，在存在干扰素-γ或肿瘤坏死因子-α的情况下，超氧阴离子（O(2)(-)）的产生、p47phox、gp91phox和p22phox的表达以及PU.1和CP-1与DNA的结合维持在血单核细胞中观察到的高水平。为了阐明PU.1在NADPH氧化酶成分表达中的作用，将竞争PU.1-DNA结合的寡核苷酸添加到培养的单核细胞中。这些寡核苷酸消除了干扰素-γ和肿瘤坏死因子-α对gp91phox和p22phox表达的维持作用，但不抑制这些细胞因子对p47phox表达和O(2)(-)产生的影响。我们的结果表明，在单核细胞中，干扰素-γ和肿瘤坏死因子-α诱导的gp91phox和p22phox表达，而不是p47phox表达，需要PU.1与gp91phox启动子结合。然而，干扰素-γ和肿瘤坏死因子-α对O(2)(-)产生的维持与它们对gp91phox和p22phox表达的影响无关。
