Katz Y, Strunk R C
Division of Pulmonary Immunology, St. Louis Children's Hospital, MO 63110.
J Immunol. 1989 Jun 1;142(11):3862-7.
IL-1 and TNF induced concentration-related increases in the synthesis of factor B, C3, and IFN-beta 2/IL-6 in human skin fibroblasts. Effects of both stimuli were apparent with concentrations as low as 0.1 ng/ml and maximal responses were observed between 1 and 10 ng/ml; only for IL-1 induction of IFN-beta 2/IL-6 was there a further increase in response up to 100 ng/ml. For factor B and C3, maximal increases induced by IL-1 and TNF were similar: 119- and 109-fold for factor B and 15-fold and 11-fold for C3, respectively. Although both IL-1 and TNF increase synthesis of factor B and C3 in hepatocytes, the increases observed in fibroblasts were approximately 50- and 8-fold more for factor B and C3, respectively. Neither protein synthesis nor mRNA for IFN-beta 2/IL-6 was present in HepG2 cells either before or after stimulation with IL-1 or TNF. In contrast to the similarities between the effects of IL-1 and TNF on synthesis of factor B, C3, and IFN-beta 2/IL-6, only TNF increased synthesis of factor H. Because TNF induces membrane IL-1 in fibroblasts, it is possible to speculate that the effects of TNF on fibroblasts are due to induction of IL-1. An autocrine action of TNF through IL-1 is possible for TNF-induced synthesis of IFN-beta 2/IL-6, but the effects of TNF on synthesis of factor B, C3, and factor H indicated that TNF has effects on fibroblasts separate from IL-1. The effects of IL-1 and TNF on the synthesis of factor B and C3 in fibroblasts may be a part of an acute phase response occurring at a local level. However, the large responses in synthesis of factor B and C3 to IL-1 and TNF may suggest that factor B and C3 have a role, as yet undescribed, in tissues in addition to the role these proteins are known to play in inflammation.
白细胞介素-1（IL-1）和肿瘤坏死因子（TNF）可诱导人皮肤成纤维细胞中B因子、C3以及干扰素-β2/白细胞介素-6（IFN-β2/IL-6）的合成呈浓度依赖性增加。两种刺激物的作用在低至0.1 ng/ml的浓度时就很明显，在1至10 ng/ml之间观察到最大反应；仅对于IL-1诱导IFN-β2/IL-6而言，在高达100 ng/ml时反应会进一步增加。对于B因子和C3，IL-1和TNF诱导的最大增加倍数相似：B因子分别为119倍和109倍，C3分别为15倍和11倍。尽管IL-1和TNF均能增加肝细胞中B因子和C3的合成，但在成纤维细胞中观察到的B因子和C3的增加分别约为肝细胞中的50倍和8倍。在用IL-1或TNF刺激之前或之后，HepG2细胞中均不存在IFN-β2/IL-6的蛋白质合成或信使核糖核酸（mRNA）。与IL-1和TNF对B因子、C3以及IFN-β2/IL-6合成的作用相似性不同，只有TNF增加了H因子的合成。由于TNF可诱导成纤维细胞中的膜IL-1，因此可以推测TNF对成纤维细胞的作用是由于诱导了IL-1。TNF通过IL-1的自分泌作用可能参与TNF诱导的IFN-β2/IL-6合成，但TNF对B因子、C3以及H因子合成的作用表明TNF对成纤维细胞具有独立于IL-1的作用。IL-1和TNF对成纤维细胞中B因子和C3合成的作用可能是局部发生的急性期反应的一部分。然而，B因子和C3合成对IL-1和TNF的大量反应可能表明，除了已知这些蛋白质在炎症中发挥的作用外，B因子和C3在组织中还具有尚未描述的作用。
