Lehmmann V, Benninghoff B, Dröge W
Deutsches Kresbsforschungszentrum Institut für Immunologie und Genetik, Heidelberg, Federal Republic of Germany.
J Immunol. 1988 Jul 15;141(2):587-91.
Human rTNF-alpha stimulates the metabolism of murine peritoneal macrophages as demonstrated by an increased consumption of arginine and an increased release of L-ornithine. This TNF-mediated effect is augmented by several substances that raise the intracellular concentration of cAMP, including PGE2, cholera toxin, and dibutyryl-cAMP. TNF also stimulates the endogenous production of PGE2 in cultures of peritoneal macrophages. The addition of the cyclo-oxygenase inhibitor, indomethacin, suppresses the TNF-mediated metabolic activation of macrophages, and this suppressive effect of indomethacin is overcome if exogenous PGE2 or cholera toxin is added to the culture. Taken together, the experiments indicate that the TNF-induced production of PGE2 and the PGE2-induced increase of the intracellular cAMP concentration are essential elements of an auto-regulatory loop that controls the magnitude of the TNF-mediated effect in the macrophage.
人源肿瘤坏死因子-α（rTNF-α）可刺激小鼠腹腔巨噬细胞的代谢，这表现为精氨酸消耗增加以及L-鸟氨酸释放增多。几种能提高细胞内cAMP浓度的物质（包括前列腺素E2（PGE2）、霍乱毒素和二丁酰环磷腺苷（dibutyryl-cAMP））可增强这种由肿瘤坏死因子介导的效应。肿瘤坏死因子还能刺激腹腔巨噬细胞培养物中PGE2的内源性产生。添加环氧化酶抑制剂吲哚美辛可抑制肿瘤坏死因子介导的巨噬细胞代谢激活，并且如果向培养物中添加外源性PGE2或霍乱毒素，吲哚美辛的这种抑制作用会被克服。综上所述，这些实验表明，肿瘤坏死因子诱导的PGE2产生以及PGE2诱导的细胞内cAMP浓度升高是一个自动调节环路的关键要素，该环路控制着肿瘤坏死因子在巨噬细胞中介导效应的强度。
