In vitro and in vivo calcitonin I gene expression in parenchymal cells:: A novel product of human adipose tissue
In vitro and in vivo calcitonin I gene expression in parenchymal cells:: A novel product of human adipose tissue
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DOI：
10.1210/en.2003-0854
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发表时间：
2003-12-01
期刊：
影响因子：
4.8
通讯作者：
Müller, B
中科院分区：
文献类型：
--
作者：
Linscheid, P;Seboek, D;Müller, B
包括降钙素原(ProCT)在内的降钙素前体(CTPR)的循环水平在人类脓毒症中增加了数千倍，免疫中和治疗提高了这种疾病的两种动物模型的存活率。在这里，我们分析了炎症介导的降钙素I基因(CALC I)在原代培养的人脂肪细胞以及不同血清ProCT水平的感染和未感染患者的脂肪组织中的表达。在体外分化的脂肪细胞中，内毒素(内毒素)作用6h后，脂肪细胞CTmRNA表达增加24倍(P<；0.05)，IL-1β作用6h后增加37倍(P<；0.05)，培养上清液中ProCT蛋白分泌量增加13.5倍(P<；0.01)，IL-1β作用48h后增加15.2倍(P<；0.01)。IL-1β介导的ProCT释放在与干扰素-γ(IFNGamma)联合给药时被抑制了89%。在感染和血清ProCT显著升高的患者中，脂肪组织活检组织中检测到CT mRNA。因此，我们证明ProCT是一种新的脂肪组织分泌产物，它被怀疑在脓毒症和炎症中介导了有害的影响。干扰素对IL-1β诱导的CT mRNA表达和ProCT分泌的抑制作用可能解释了先前的观察结果，即与细菌感染相比，全身病毒患者血清ProCT浓度升高较少。
Circulating levels of calcitonin precursors (CTpr), including procalcitonin (ProCT), increase up to several thousand-fold in human sepsis, and immunoneutralization improves survival in two animal models of this disease. Herein, we analyzed inflammation-mediated calcitonin I gene (CALC I) expression in human adipocyte primary cultures and in adipose tissue samples from infected and noninfected patients with different levels of serum ProCT. In ex vivo differentiated adipocytes, the expression of CT mRNA increased 24-fold (P < 0.05) after the administration of Escherichia coli endotoxin (lipopolysaccharide) and 37-fold (P < 0.05) after IL-1beta administration by 6 h. ProCT protein secretion into culture supernatant increased 13.5-fold (P < 0.01) with lipopolysaccharide treatment and 15.2-fold (P < 0.01) with IL-1beta after 48 h. In coculture experiments, adipocyte CT mRNA expression was evoked by E. coli activated macrophages in which CT mRNA was undetectable. The marked IL-1beta-mediated ProCT release was inhibited by 89% during coadministration with interferon-gamma (IFNgamma). In patients with infection and markedly increased serum ProCT, CT mRNA was detected in adipose tissue biopsies. Hence, we demonstrate that ProCT, which is suspected to mediate deleterious effects in sepsis and inflammation, is a novel product of adipose tissue secretion. The inhibiting effect of IFNgamma on IL-1beta-induced CT mRNA expression and on ProCT secretion might explain previous observations that serum ProCT concentrations increase less in systemic viral compared with bacterial infections.