Standiford T J, Lindsten T, Thompson C B, Strieter R M, Kunkel S L
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Pathobiology. 1992;60(2):100-7. doi: 10.1159/000163706.
Tumor necrosis factor-alpha (TNF-alpha), a product of both mononuclear phagocytes and T lymphocytes, is an important proximal mediator of a number of acute and chronic inflammatory disease states. In this investigation we examine the regulatory effects of the lymphocyte product interleukin-4 (IL-4) on the gene expression of TNF-alpha from stimulated human peripheral blood monocytes (PBM) and T lymphocytes. We demonstrated the dose-dependent suppression of TNF-alpha mRNA and protein synthesis from lipopolysaccharide-treated PBM by IL-4. The suppressive effects of IL-4 appear to be dependent upon de novo protein synthesis, as cycloheximide abrogated the IL-4-induced reduction in TNF-alpha mRNA levels from PBM. In contrast to the suppressive effects of IL-4 on PBM-derived cytokine expression, IL-4 did not alter TNF-alpha mRNA expression from alpha-Cd3 or PMA + alpha-CD-28-treated T lymphocytes. Moreover, IL-2 mRNA expression from similarly treated T lymphocytes was unaltered by IL-4. Our findings demonstrate that disparity exists in the regulation of TNF-alpha gene expression from different immune cell populations which may have important implications in the evolution of acute and chronic inflammatory responses.
肿瘤坏死因子-α（TNF-α）是单核吞噬细胞和T淋巴细胞的产物，是许多急性和慢性炎症性疾病状态的重要近端介质。在本研究中，我们检测了淋巴细胞产物白细胞介素-4（IL-4）对刺激的人外周血单核细胞（PBM）和T淋巴细胞中TNF-α基因表达的调节作用。我们证明了IL-4对脂多糖处理的PBM中TNF-α mRNA和蛋白质合成具有剂量依赖性抑制作用。IL-4的抑制作用似乎依赖于从头合成蛋白质，因为放线菌酮消除了IL-4诱导的PBM中TNF-α mRNA水平的降低。与IL-4对PBM来源的细胞因子表达的抑制作用相反，IL-4不会改变α-Cd3或PMA +α-CD-28处理的T淋巴细胞中TNF-α mRNA的表达。此外，IL-4不会改变经类似处理的T淋巴细胞中IL-2 mRNA的表达。我们的研究结果表明，不同免疫细胞群体对TNF-α基因表达的调节存在差异，这可能对急性和慢性炎症反应的演变具有重要意义。
