Fulton S A, Cross J V, Toossi Z T, Boom W H
Division of Infectious Diseases, Case Western Reserve University, Cleveland, Ohio, USA.
J Infect Dis. 1998 Oct;178(4):1105-14. doi: 10.1086/515698.
Regulation of interleukin (IL)-12 production by coexpression of tumor necrosis factor (TNF)-alpha, IL-10, and transforming growth factor (TGF)-beta in human monocytes infected with Mycobacterium tuberculosis H37Ra was analyzed. Also, since IL-12 induces interferon (IFN)-gamma, the effect of IFN-gamma on IL-12 expression was examined. IL-12 mRNA was measured by reverse transcriptase-polymerase chain reaction and IL-12 protein by ELISA. IL-12 p35 mRNA was constitutive and inducible. IL-12 p70 protein paralleled IL-12 p40 protein expression. TNF-alpha protein expression occurred earlier than IL-12 p40 protein but was not required for IL-12 induction. Addition or neutralization of TGF-beta did not significantly alter IL-12 induction. In contrast, recombinant IL-10 reduced IL-12 and neutralization of IL-10 minimally enhanced IL-12. A pronounced increase in IL-12 followed IFN-gamma pretreatment, which selectively up-regulated IL-12 p35 mRNA. Further understanding of operative cytokine networks during M. tuberculosis infection may improve strategies for vaccine development and immunotherapy.
分析了肿瘤坏死因子（TNF）-α、白细胞介素（IL）-10和转化生长因子（TGF）-β共表达对感染结核分枝杆菌H37Ra的人单核细胞中IL-12产生的调节作用。此外，由于IL-12可诱导干扰素（IFN）-γ，因此检测了IFN-γ对IL-12表达的影响。通过逆转录-聚合酶链反应测量IL-12 mRNA，通过酶联免疫吸附测定法测量IL-12蛋白。IL-12 p35 mRNA是组成性的且可诱导。IL-12 p70蛋白与IL-12 p40蛋白表达平行。TNF-α蛋白表达早于IL-12 p40蛋白，但IL-12诱导不需要它。添加或中和TGF-β并未显著改变IL-12诱导。相反，重组IL-10降低IL-12，而中和IL-10则使IL-12略有增强。IFN-γ预处理后IL-12显著增加，这选择性地上调了IL-12 p35 mRNA。进一步了解结核分枝杆菌感染期间起作用的细胞因子网络可能会改善疫苗开发和免疫治疗策略。
