Rothe H, Hartmann B, Geerlings P, Kolb H
Diabetes Research Institute, Heinrich- Heine University of Düsseldorf, Germany.
Biochem Biophys Res Commun. 1996 Jul 5;224(1):159-63. doi: 10.1006/bbrc.1996.1000.
Interleukin-12 is a heterodimeric cytokine, mainly produced by macrophages. In our present study we demonstrate that interleukin-12 expression is regulated by nitric oxide. Incubation of the macrophage cell line IC 21 with interferon-gamma gave rise to both interleukin-12 p40 mRNA and nitric oxide production. The concurrent addition of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine inhibited nitrite production and in parallel completely suppressed interleukin-12 p40 mRNA formation. This indicated that endogenous nitric oxide synthase activity was required for IL-12 p40 gene expression. Exposure of the cells towards the nitric oxide generating compounds nitroprusside or S-nitroso-N-acetyl-penicillamine induced interleukin-12 p40 mRNA. Maximal mRNA levels were induced with nitric oxide donors at 1 microM concentration. We conclude that nitric oxide may exert an autoregulatory and paracrine control of interleukin-12 gene expression.
白细胞介素-12是一种异二聚体细胞因子，主要由巨噬细胞产生。在我们目前的研究中，我们证明白细胞介素-12的表达受一氧化氮调节。用γ干扰素培养巨噬细胞系IC 21可产生白细胞介素-12 p40 mRNA和一氧化氮。同时添加一氧化氮合酶抑制剂N(G)-单甲基-L-精氨酸可抑制亚硝酸盐的产生，同时完全抑制白细胞介素-12 p40 mRNA的形成。这表明内源性一氧化氮合酶活性是IL-12 p40基因表达所必需的。用产生一氧化氮的化合物硝普钠或S-亚硝基-N-乙酰青霉胺处理细胞可诱导白细胞介素-12 p40 mRNA。在1 microM浓度的一氧化氮供体作用下可诱导出最大mRNA水平。我们得出结论，一氧化氮可能对白介素-12基因表达发挥自调节和旁分泌控制作用。
