Staples K J, Bergmann M, Barnes P J, Newton R
Department of Thoracic Medicine, Imperial College of Science, Technology, and Medicine, National Heart and Lung Institute, Dovehouse Street, London, SW3 6LY, United Kingdom.
Biochem Biophys Res Commun. 2000 Jul 14;273(3):811-5. doi: 10.1006/bbrc.2000.3023.
Interleukin-5 (IL-5) is a Th2 cytokine, which is implicated in the pathogenesis of eosinophilic diseases such as asthma. Peripheral blood mononuclear cells (PBMC), costimulated with phorbol 12-myristate 13-acetate (PMA) plus phytohemagglutinin (PHA) or activating antibodies to the CD3 and CD28 T-lymphocyte surface markers, produced similar patterns of IL-5 expression. However, in PMA + PHA-treated cells, 8-bromo-cAMP and PGE(2) did not affect IL-5 expression, whereas in CD3 + CD28-stimulated cells, almost total repression was observed. IL-10 failed to inhibit IL-5 mRNA from PMA + PHA-treated cells, yet reduced release by 40%. By contrast, IL-10 totally inhibited CD3 + CD28-induced IL-5 release and inhibited mRNA by 50-60%. These results highlight important biological differences in the induction of IL-5 by the nonspecific stimulus PMA + PHA and the more physiological CD3 + CD28 costimulation. Finally, the potential for downregulating Th2 responses by cAMP-elevating agents or IL-10 is demonstrated and a significant role for posttranscriptional mechanisms in the inhibition by IL-10 is suggested.
白细胞介素-5（IL-5）是一种Th2细胞因子，与哮喘等嗜酸性粒细胞疾病的发病机制有关。外周血单个核细胞（PBMC）在用佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）加植物血凝素（PHA）或针对CD3和CD28 T淋巴细胞表面标志物的活化抗体共刺激时，产生相似的IL-5表达模式。然而，在PMA + PHA处理的细胞中，8-溴-cAMP和前列腺素E2（PGE2）不影响IL-5表达，而在CD3 + CD28刺激的细胞中，观察到几乎完全抑制。IL-10不能抑制PMA + PHA处理细胞中的IL-5 mRNA，但使释放减少40%。相比之下，IL-10完全抑制CD3 + CD28诱导的IL-5释放，并使mRNA抑制50 - 60%。这些结果突出了非特异性刺激PMA + PHA和更具生理性的CD3 + CD28共刺激诱导IL-5过程中的重要生物学差异。最后，证明了通过提高cAMP的药物或IL-10下调Th2反应的潜力，并提示转录后机制在IL-10抑制中起重要作用。
