Nakagawa-Tosa N, Morimatsu M, Kawasaki M, Nakatsuji H, Syuto B, Saito M
Department of Biochemistry, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
J Vet Med Sci. 1995 Apr;57(2):219-23. doi: 10.1292/jvms.57.219.
The hepatic synthesis of acute phase proteins in ruminants has been suggested to be regulated by some mechanisms different from those in other species such as rodents and human. To explore possible regulatory factors unique to ruminants, we examined effects of interleukin (IL)-6, IL-1 and tumor necrosis factor (TNF), on haptoglobin (Hp) synthesis using a primary culture system of bovine hepatocytes. After bovine primary cultured hepatocytes were incubated in the presence of various concentrations of the cytokines, the synthesis and mRNA level of haptoglobin and albumin were measured by labeling with [35S]-methionine and immunoprecipitation, and by Northern blot analysis, respectively. Hp synthesis was dose-dependently increased by recombinant human (rh) IL-6, and also by rhTNF-alpha, but to a less extent, while it was not affected by rhIL-1 beta. The stimulatory effect is mainly pretranslational, because mRNA level of Hp changed in parallel with protein synthesis. In contrast, albumin synthesis was suppressed by these three cytokines similarly. These results are inconsistent with the previously proposed view that TNF and IL-1 overlap in their pathways leading to the transcriptional activation of many acute phase protein genes. In conclusion, there is a species-specific unique signaling system, especially for TNF, in transcriptional activation of bovine Hp gene.
反刍动物急性期蛋白的肝脏合成被认为受一些与啮齿动物和人类等其他物种不同的机制调控。为了探索反刍动物特有的可能调控因子，我们使用牛肝细胞原代培养系统研究了白细胞介素（IL）-6、IL-1和肿瘤坏死因子（TNF）对触珠蛋白（Hp）合成的影响。在用各种浓度的细胞因子孵育牛原代培养肝细胞后，分别通过用[35S]-甲硫氨酸标记和免疫沉淀以及Northern印迹分析来测量触珠蛋白和白蛋白的合成及mRNA水平。重组人（rh）IL-6以及rhTNF-α可使Hp合成呈剂量依赖性增加，但rhTNF-α的作用程度较小，而rhIL-1β对其无影响。这种刺激作用主要是在翻译前，因为Hp的mRNA水平与蛋白质合成平行变化。相反，这三种细胞因子对白蛋白合成均有类似的抑制作用。这些结果与先前提出的TNF和IL-1在导致许多急性期蛋白基因转录激活的途径中存在重叠的观点不一致。总之，在牛Hp基因的转录激活中存在物种特异性的独特信号系统，尤其是对于TNF而言。
