Narumi S, Wyner L M, Stoler M H, Tannenbaum C S, Hamilton T A
Research Institute, Cleveland Clinic Foundation, OH 44195.
J Leukoc Biol. 1992 Jul;52(1):27-33. doi: 10.1002/jlb.52.1.27.
We have examined the tissue distribution of 10-kd inflammatory protein (IP-10) mRNA expression in C57Bl/6 mice injected intravenously (i.v.) with various inflammatory stimuli. IP-10 mRNA was strongly induced by interferon-gamma (IFN-gamma) in liver and kidney but only poorly in skin, heart, and lung. IFN-gamma had nearly equivalent access to these tissues as indicated by the distribution of radiolabeled recombinant IFN-gamma 1 h after injection. The time course of IP-10 mRNA appearance was rapid and transient in both liver and kidney; maximal expression in the liver (2 h) preceded that in the kidney (3 h) and declined rapidly thereafter in both tissues. Expression of IP-10 mRNA in the liver and kidney was highly sensitive to IFN-gamma treatment; nearly maximal stimulation occurred with injection of 500 U of IFN-gamma per mouse. Comparable stimulation of IP-10 mRNA expression in splenic macrophages required 10,000 U of IFN-gamma administered i.v., indicating that liver and kidney responses are 10- to 20-fold more sensitive. IP-10 mRNA expression in both tissues was not restricted to stimulation by IFN-gamma but was also seen with injection of lipopolysaccharide (LPS) (25 micrograms/mouse) or IFN-beta (100,000 U/mouse). Two other members of the IP-10 gene family, KC (gro) and JE (MCP-1), were expressed at lower levels under similar treatment conditions. Analysis of IP-10 mRNA distribution in the liver and kidney by in situ hybridization indicated that expression in both tissues was most prominent in the reticuloendothelial cell system, particularly in the endothelial lining of the microvascular circulation. Although the function of the IP-10 gene product has not been defined, these results suggest that it may play an important role in the response of both the liver and kidney to systemic inflammation.
我们检测了静脉注射（i.v.）各种炎症刺激剂的C57Bl/6小鼠中10-kd炎症蛋白（IP-10）mRNA表达的组织分布情况。γ干扰素（IFN-γ）可在肝脏和肾脏中强烈诱导IP-10 mRNA表达，但在皮肤、心脏和肺中诱导作用较弱。注射放射性标记的重组IFN-γ 1小时后的分布情况表明，IFN-γ进入这些组织的情况几乎相同。IP-10 mRNA在肝脏和肾脏中出现的时间进程迅速且短暂；肝脏中的最大表达（2小时）先于肾脏（3小时），之后在两个组织中均迅速下降。肝脏和肾脏中IP-10 mRNA的表达对IFN-γ处理高度敏感；每只小鼠注射500 U的IFN-γ时，几乎可产生最大刺激。静脉注射10,000 U的IFN-γ才能在脾巨噬细胞中产生类似的IP-10 mRNA表达刺激，这表明肝脏和肾脏的反应敏感性要高10至20倍。两个组织中IP-10 mRNA的表达不仅限于IFN-γ刺激，注射脂多糖（LPS）（25微克/小鼠）或IFN-β（100,000 U/小鼠）时也可观察到。在相似的处理条件下，IP-10基因家族的另外两个成员KC（gro）和JE（MCP-1）的表达水平较低。通过原位杂交分析肝脏和肾脏中IP-10 mRNA的分布表明，两个组织中的表达在网状内皮细胞系统中最为显著，尤其是在微血管循环的内皮衬里。尽管IP-10基因产物的功能尚未明确，但这些结果表明它可能在肝脏和肾脏对全身炎症的反应中起重要作用。
