Cloning, expression and initial characterisation of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10)
Cloning, expression and initial characterisation of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10)
复制标题
DOI：
10.1038/sj.gene.6363714
复制
发表时间：
2000-10-01
影响因子：
5
通讯作者：
Kotenko, SV
中科院分区：
文献类型：
--
作者：
Gallagher, G;Dickensheets, H;Kotenko, SV
白细胞介素 - 10（IL - 10）是一种具有重要免疫调节功能的多效性细胞因子，其作用影响免疫系统中许多细胞类型的活动。我们在此报道了一种基因及其相应cDNA的鉴定和克隆，该基因编码一种新的IL - 10同源物，被命名为IL - 19。IL - 19与IL - 10有21%的氨基酸同一性。IL - 19的外显子/内含子结构与人IL - 10基因相似，在IL - 19 cDNA的编码区内包含5个外显子和4个内含子。至少有两种不同的IL - 19 mRNA，它们的5' - 序列不同，这表明在IL - 19基因编码部分的5' - 序列中存在一个内含子。较长的5' - 序列包含一个可选择的起始ATG密码子，它与其余编码序列同框。经脂多糖（LPS）处理可诱导单核细胞中IL - 19 mRNA的表达。与IL - 10 mRNA的表达相比，LPS刺激的单核细胞中IL - 19 mRNA的出现稍有延迟：刺激后2小时可检测到显著水平的IL - 10 mRNA，而直到4小时才能检测到IL - 19 mRNA。用IL - 4或IL - 13处理单核细胞不会诱导IL - 19的从头表达，但这些细胞因子确实增强了LPS刺激的单核细胞中IL - 19基因的表达。此外，粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）能够直接诱导单核细胞中IL - 19基因的表达。IL - 19不通过经典的IL - 10受体复合物结合或发出信号，这表明存在一种IL - 19特异性受体复合物，其身份仍有待发现。
Interleukin-10 (IL-10) is a pleiotropic cytokine with important immunoregulatory functions whose actions influence activities of many of the cell-types in the immune system. We report here identification and cloning of a gene and corresponding cDNAs encoding a novel homologue of IL-IO, designated IL-19. IL-19 shares 21% amino acid identity with IL-10. The exon/intron structure of IL-19 is similar to that of the human IL-IO gene, comprising five exons and four introns within the coding region of the IL-19 cDNA. There are at least two distinct IL-19 mRNA species that differ in their 5'-sequences, suggesting the existence of an intron in the 5'-sequences of coding portion of the IL-19 gene. The longer 5'-sequence contains an alternative initiating ATG codon that is in-frame with the rest of the coding sequence. The expression of IL-19 mRNA can be induced in monocytes by LPS-treatment. The appearance of IL-19 mRNA in LPS-stimulated monocytes was slightly delayed compared to expression of IL-10 mRNA: significant levels of IL-10 mRNA were detectable at 2 h post-stimulation, whereas IL-19 mRNA was not detectable until 4 h. Treatment of monocytes with IL-4 or IL-13 did not induce de novo expression of IL-19, but these cytokines did potentiate IL-19 gene expression in LPS-stimulated monocytes. In addition, GM-CSF was capable of directly inducing IL-19 gene expression in monocytes. IL-19 does nor bind or signal through the canonical IL-10 receptor complex, suggesting existence of an IL-19 specific receptor complex, the identity of which remains to be discovered.