Ulich T R, Guo K Z, Irwin B, Remick D G, Davatelis G N
Department of Pathology, University of California, Irvine School of Medicine 92717.
Am J Pathol. 1990 Nov;137(5):1173-85.
Tumor necrosis factor alpha (TNF alpha) mRNA is present in a preformed intracellular pool in the spleen, liver, and small bowel of naive rats. Endotoxin (Salmonella typhus lipopolysaccharide) injected intravenously induces little or no increase in whole-organ TNF mRNA levels at 15', 30', 1 degree, 2 degrees, or 4 degrees, whereas serum TNF levels are markedly elevated at 1 and 2 hours. Dexamethasone pretreatment of rats suppresses LPS-induced serum TNF concentrations, but does not suppress TNF mRNA levels in the spleen or bowel. Tachyphylaxis experiments demonstrate that a second injection of endotoxin 2 hours after an initial injection fails to induce a second peak of serum TNF, although TNF mRNA levels in the spleen and bowel remain at the levels found in naive rats. Corynebacterium parvum upregulates endotoxin-induced serum TNF release and intravenous injection of IL-1 induces the release of serum TNF but neither alters whole-organ TNF mRNA levels. Interleukin-1 alpha (IL-1 alpha) mRNA was not constitutively detected in whole-organ RNA preparations of the spleen, liver, and small bowel of naive rats. Endotoxin induces IL-1 alpha mRNA most easily appreciated in the spleen beginning at 1 hour, peaking at 2 to 4 hours, and disappearing by 6 hours. Interleukin-1 beta (IL-1 beta) mRNA was not constitutively detected in the organs examined or was present in small amounts. Endotoxin induces IL-1 beta mRNA beginning at 0.5 hours, peaking at 1 hour, and disappearing by 6 hours. Dexamethasone pretreatment prevents the LPS-induced appearance of IL-1 alpha mRNA and suppresses but does not completely inhibit the appearance of IL-1 beta mRNA. C. parvum upregulates endotoxin-induced IL-1 mRNA expression. Intravenous injection of TNF or IL-1 both induce IL-1 mRNA expression. In conclusion, TNF mRNA is constitutively expressed and TNF mRNA levels as analyzed in whole-organ RNA preparations do not change in concert with serum TNF protein levels during conditions of endotoxemia, dexamethasone treatment, tachyphylaxis, priming with C. parvum, or after injection of IL-1. In contrast, IL-1 mRNA expression during endotoxemia, dexamethasone treatment, priming with C. parvum, or after injection of TNF or IL-1 shows clear increases and decreases in whole-organ RNA preparations.
肿瘤坏死因子α（TNFα）mRNA存在于未接触过抗原的大鼠脾脏、肝脏和小肠预先形成的细胞内池中。静脉注射内毒素（鼠伤寒沙门氏菌脂多糖）在15分钟、30分钟、1小时、2小时或4小时时，全器官TNF mRNA水平几乎没有增加或没有增加，而血清TNF水平在1小时和2小时时显著升高。大鼠地塞米松预处理可抑制脂多糖诱导的血清TNF浓度，但不抑制脾脏或肠道中的TNF mRNA水平。快速耐受实验表明，在初次注射2小时后再次注射内毒素不能诱导血清TNF出现第二个峰值，尽管脾脏和肠道中的TNF mRNA水平仍保持在未接触过抗原的大鼠中的水平。短小棒状杆菌上调内毒素诱导的血清TNF释放，静脉注射白细胞介素-1（IL-1）可诱导血清TNF释放，但两者均不改变全器官TNF mRNA水平。在未接触过抗原的大鼠脾脏、肝脏和小肠的全器官RNA制剂中未组成性检测到白细胞介素-1α（IL-1α）mRNA。内毒素诱导IL-1α mRNA，在脾脏中最早在1小时出现，2至4小时达到峰值，6小时时消失。在所检查的器官中未组成性检测到白细胞介素-1β（IL-1β）mRNA或其含量很少。内毒素诱导IL-1β mRNA，在0.5小时开始出现，1小时达到峰值，6小时时消失。地塞米松预处理可防止脂多糖诱导的IL-1α mRNA出现，并抑制但不能完全抑制IL-1β mRNA的出现。短小棒状杆菌上调内毒素诱导的IL-1 mRNA表达。静脉注射TNF或IL-1均可诱导IL-1 mRNA表达。总之，TNF mRNA组成性表达，在内毒素血症、地塞米松治疗、快速耐受、短小棒状杆菌致敏或注射IL-1后，全器官RNA制剂中分析的TNF mRNA水平与血清TNF蛋白水平不一致。相反，在内毒素血症、地塞米松治疗、短小棒状杆菌致敏或注射TNF或IL-1后，全器官RNA制剂中IL-1 mRNA表达有明显的增加和减少。
