White J E, Tsan M F
Research Service, Samuel S. Stratton Department of Veterans Affairs Medical Center, Albany, NY 12208.
Am J Physiol. 1994 Jun;266(6 Pt 1):L664-71. doi: 10.1152/ajplung.1994.266.6.L664.
We have previously demonstrated that intratracheal (IT) but not intraperitoneal (IP) administration of 5 micrograms tumor necrosis factor (TNF) or interleukin-1 (IL-1) selectively enhances pulmonary Mn superoxide dismutase (Mn SOD) mRNA, leading to increased Mn SOD protein and enzyme activity, and protects rats against O2 toxicity. In this study, we demonstrated that enhancement of pulmonary Mn SOD mRNA by TNF or IL-1 was highly dependent on the route of administration. IT insufflation of 5 micrograms TNF or IL-1 selectively enhanced levels of pulmonary but not splenic or renal Mn SOD mRNA. In contrast, IP or intravenous (i.v.) administration of TNF (5 micrograms) or IL-1 (5, 20, or 50 micrograms) had little or no effect on levels of Mn SOD mRNA in the lung, spleen, or kidney. Both TNF and IL-1, whether given by IT, IP, or i.v. administration, had no effect on levels of Cu, Zn SOD mRNA. IP administration of 2 mg/kg actinomycin D 2 h before IT insufflation of IL-1 paradoxically increased the level of pulmonary Mn SOD mRNA without affecting the level of Cu,Zn SOD or beta-actin mRNA in IL-1-treated rats. Nuclear runoff transcription assay revealed that IT insufflation of IL-1 enhanced the rate on MN SOD but not Cu,Zn SOD mRNA synthesis. We conclude that IL-1-induced increase in pulmonary Mn SOD mRNA is at least in part regulated at the transcriptional level.
我们之前已经证明，气管内（IT）而非腹腔内（IP）给予5微克肿瘤坏死因子（TNF）或白细胞介素-1（IL-1）可选择性增强肺锰超氧化物歧化酶（Mn SOD）mRNA，导致Mn SOD蛋白和酶活性增加，并保护大鼠免受氧毒性。在本研究中，我们证明TNF或IL-1对肺Mn SOD mRNA的增强高度依赖于给药途径。气管内注入5微克TNF或IL-1可选择性提高肺而非脾或肾的Mn SOD mRNA水平。相比之下，腹腔内或静脉内（i.v.）给予TNF（5微克）或IL-1（5、20或50微克）对肺、脾或肾中Mn SOD mRNA水平几乎没有影响。无论是通过气管内、腹腔内还是静脉内给药，TNF和IL-1对铜锌超氧化物歧化酶（Cu，Zn SOD）mRNA水平均无影响。在气管内注入IL-1前2小时腹腔内给予2mg/kg放线菌素D，反常地增加了IL-1处理大鼠的肺Mn SOD mRNA水平，而不影响Cu，Zn SOD或β-肌动蛋白mRNA水平。核转录分析显示，气管内注入IL-1可提高Mn SOD而非Cu，Zn SOD mRNA的合成速率。我们得出结论，IL-1诱导的肺Mn SOD mRNA增加至少部分是在转录水平上调节的。
