Weltman J K, Karim A S
Department of Medicine, Brown University School of Medicine, Providence, Rhode Island, USA.
Allergy Asthma Proc. 1998 Sep-Oct;19(5):257-61. doi: 10.2500/108854198778557782.
Interleukin-5 (IL-5) is the predominant cytokine associated with antigen-induced eosinophilic inflammation in the lung. The activation of TH2 cells leads to the production of IL-5. The proeosinophilic effects of IL-5 include 1) enhanced replication and differentiation of eosinophilic myelocytes; 2) enhanced degranulation of eosinophils; 3) prolonged survival time of eosinophils; and 4) enhanced adhesion of eosinophils. The effects of IL-5 are mediated via the interaction of IL-5 with receptors (Il-5R) expressed on the eosinophil cell membrane. Intracellular signaling produced by occupation of the IL-5R by IL-5 occurs via the JAK-STAT system. IL-5 is a 45kD glycoprotein that consists of two identical polypeptide chains. The 5'-promoter region of the IL-5 gene contains elements that are down-regulated by glucocorticoids. A 16-mer deoxyoligonucleotide, antisense to IL-5 mRNA and with two phosphorothioate modifications, produced, at 20 micromolar concentration, complete inhibition of IL-5 secretion by human peripheral blood mononuclear cells. The targeted 16-mer sequence of the IL-5 mRNA did not display complete homology with any other known human gene sequences. These results suggest that the 16-mer phosphorothioate antisense IL-5 provides the basis for a non-glucocorticoid, sequence-specific inhibitor of IL-5.
白细胞介素-5（IL-5）是与肺部抗原诱导的嗜酸性粒细胞炎症相关的主要细胞因子。TH2细胞的激活导致IL-5的产生。IL-5的促嗜酸性粒细胞作用包括：1）增强嗜酸性粒细胞髓细胞的复制和分化；2）增强嗜酸性粒细胞的脱颗粒作用；3）延长嗜酸性粒细胞的存活时间；4）增强嗜酸性粒细胞的黏附。IL-5的作用是通过IL-5与嗜酸性粒细胞细胞膜上表达的受体（Il-5R）相互作用介导的。IL-5占据IL-5R所产生的细胞内信号通过JAK-STAT系统发生。IL-5是一种45kD的糖蛋白，由两条相同的多肽链组成。IL-5基因的5'-启动子区域含有受糖皮质激素下调的元件。一种16聚体脱氧寡核苷酸，与IL-5 mRNA反义且有两个硫代磷酸酯修饰，在20微摩尔浓度时，可完全抑制人外周血单个核细胞分泌IL-5。IL-5 mRNA的靶向16聚体序列与任何其他已知的人类基因序列均未显示出完全同源性。这些结果表明，16聚体硫代磷酸酯反义IL-5为非糖皮质激素、序列特异性的IL-5抑制剂提供了基础。
