Sonouchi K, Hamilton T A, Tannenbaum C S, Tubbs R R, Bukowski R, Finke J H
Department of Immunology, Cleveland Clinic Foundation, OH 46195.
Am J Pathol. 1994 Apr;144(4):747-55.
The expression of three chemoattractant cytokine (chemokine) messenger (m)RNAs in the murine renal cell carcinoma (RENCA) from mice treated with a combination of interferon-alpha (IFN-alpha) and interleukin-2 was examined and related to tumor infiltration by inflammatory leukocytes. Using a semi-quantitative reverse transcriptase polymerase chain reaction assay, mRNAs encoding the KC, JE, and IP-10 genes were all elevated in tumor tissue from mice treated systemically with IFN-alpha/interleukin-2 for 4 days. Similarly, the mRNA for tumor necrosis factor-alpha (TNF-alpha) was also increased in tumors from treated as compared to control animals. The same tumors showed a significant increase in Mac-1+ leukocytes, which correlated well with the increase in chemokine and TNF-alpha gene expression. The renal cell carcinoma tumor itself may be responsible for the expression of chemokine genes in the tumor bed following cytokine therapy. Cultures of freshly explanted RENCA cells expressed significant levels of chemokine mRNAs when stimulated in vitro with IFN alpha, IFN gamma, and/or interleukin-2, demonstrating that this tumor cell has potential for expression of these genes in vivo. In contrast, TNF-alpha expression was not detected in cultured tumor cells. Thus TNF-alpha may be expressed by infiltrating monocytes following exposure to recombinant cytokine therapy.
研究了用α干扰素（IFN-α）和白细胞介素-2联合治疗的小鼠肾细胞癌（RENCA）中三种趋化性细胞因子（趋化因子）信使（m）RNA的表达，并将其与炎性白细胞的肿瘤浸润相关联。使用半定量逆转录聚合酶链反应分析，在用IFN-α/白细胞介素-2全身治疗4天的小鼠的肿瘤组织中，编码KC、JE和IP-10基因的mRNA均升高。同样，与对照动物相比，治疗组肿瘤中肿瘤坏死因子-α（TNF-α）的mRNA也增加。相同的肿瘤显示Mac-1 +白细胞显著增加，这与趋化因子和TNF-α基因表达的增加密切相关。肾细胞癌肿瘤本身可能是细胞因子治疗后肿瘤床中趋化因子基因表达的原因。当用IFN-α、IFN-γ和/或白细胞介素-2体外刺激时，新鲜分离的RENCA细胞培养物表达显著水平的趋化因子mRNA，表明这种肿瘤细胞在体内具有表达这些基因的潜力。相反，在培养的肿瘤细胞中未检测到TNF-α表达。因此，TNF-α可能在暴露于重组细胞因子治疗后由浸润的单核细胞表达。
