Vannier E, de Waal Malefyt R, Salazar-Montes A, de Vries J E, Dinarello C A
Department of Medicine, Tufts University of Medicine, Boston, Masachusetts USA.
Blood. 1996 Apr 15;87(8):3307-15.
Interleukin-13 (IL-13) belongs to the IL-4 gene family. Like IL-4, IL-13 induces IL-1 receptor antagonist (IL-1Ra) synthesis with no effect on IL-1beta synthesis. We investigated whether IL-13 induces IL-1Ra synthesis via a pathway similar to IL-4. In human peripheral blood mononuclear cells, IL-13 (1 to 100 ng/mL alone induced IL-1Ra synthesis in a dose-dependent manner. A single amino acid mutant form of IL-4 (hIL4.Yl24D) induced IL-1Ra synthesis, acting as a partial agonist. However, hIL-4.Yl24D inhibited IL-1Ra synthesis induced by either IL-4 or IL-13. IL-13 alone induced accumulation of IL-1Ra mRNA. Furthermore, IL-13 reduced steady- state levels for IL-1beta mRNA but enhanced those for IL-1Ra mRNA in cells stimulated with lipopolysaccharide (LPS) or IL-1alpha. Accordingly, IL-13 suppressed IL-1beta synthesis but enhanced IL-1Ra synthesis in these cells. IL-13 reduced the stability of IL-1beta mRNA (2.9 v 1.7 hours) but failed to modify the stability of IL-1Ra mRNA (2.7 v 2.5 hours). Moreover, IL-13 induced transcriptional activation of the IL-1Ra gene, but reduced IL-1beta gene transcription. Our results suggest that the commonality between IL-13 and IL-4 in inducing IL-1Ra synthesis results from the engagement of a subunit common to both receptors.
白细胞介素-13（IL-13）属于IL-4基因家族。与IL-4一样，IL-13可诱导白细胞介素-1受体拮抗剂（IL-1Ra）的合成，而对IL-1β的合成没有影响。我们研究了IL-13是否通过与IL-4相似的途径诱导IL-1Ra的合成。在人外周血单个核细胞中，单独使用IL-13（1至100 ng/mL）可剂量依赖性地诱导IL-1Ra的合成。IL-4的单氨基酸突变形式（hIL4.Yl24D）可诱导IL-1Ra的合成，起到部分激动剂的作用。然而，hIL-4.Yl24D可抑制由IL-4或IL-13诱导的IL-1Ra的合成。单独的IL-13可诱导IL-1Ra mRNA的积累。此外，在脂多糖（LPS）或IL-1α刺激的细胞中，IL-13可降低IL-1β mRNA的稳态水平，但可提高IL-1Ra mRNA的稳态水平。因此，IL-13在这些细胞中可抑制IL-1β的合成，但可增强IL-1Ra的合成。IL-13可降低IL-1β mRNA的稳定性（2.9对1.7小时），但未能改变IL-1Ra mRNA的稳定性（2.7对2.5小时）。此外，IL-13可诱导IL-1Ra基因的转录激活，但可降低IL-1β基因的转录。我们的结果表明，IL-13和IL-4在诱导IL-1Ra合成方面的共性源于两种受体共有的一个亚基的结合。
