Identification and initial characterization of four novel members of the interleukin-1 family
Identification and initial characterization of four novel members of the interleukin-1 family
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DOI：
10.1074/jbc.275.14.10308
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发表时间：
2000-04-07
影响因子：
4.8
通讯作者：
Young, PR
中科院分区：
文献类型：
--
作者：
Kumar, S;McDonnell, PC;Young, PR
白细胞介素 - 1（IL - 1）、成纤维细胞生长因子（FGFs）及其同源物是分泌型因子，它们具有共同的β - 桶状结构，并通过与细胞外结构域中具有免疫球蛋白样折叠的细胞表面受体结合作用于靶细胞。虽然已经发现了FGF家族的众多成员，但IL - 1家族成员数量一直较少，且其数量少于IL - 1受体同源物。通过对表达序列标签数据库的搜索，我们现在已经鉴定出另外四种IL - 1同源物，即IL - 1H1、IL - 1H2、IL - 1H3和IL - 1H4。像大多数其他IL - 1/FGF一样，这些蛋白质不含有疏水引导序列。IL - 1H4具有前肽序列，而IL - 1H1、IL - 1H2和IL - 1H3仅编码成熟蛋白。圆二色光谱和热稳定性分析表明，1H1的折叠方式与IL - 1ra相似。这些新的同源物在哺乳动物中没有广泛表达。IL - 1H1仅在胎盘和食管的鳞状上皮中组成性表达。然而，IL - 1H1可在体外由干扰素 - γ和肿瘤坏死因子 - α在角质形成细胞中诱导产生，也可在体内通过接触性超敏反应或单纯疱疹病毒感染诱导产生。这表明IL - 1H1可能参与免疫介导的疾病过程的发病机制。四种新的IL - 1同源物的发现表明，IL - 1家族比之前认为的要大得多。
Interleukin-1 (IL-1), fibroblast growth factors (FGFs), and their homologues are secreted factors that share a common p-barrel structure and act on target cells by binding to cell surface receptors with immunoglobulinlike folds in their extracellular domain. While numerous members of the FGF family have been discovered, the IL-1 family has remained small and outnumbered by IL-1 receptor homologues, From expressed sequence tag data base searches, we have now identified four additional IL-1 homologues, IL-1H1, IL-1H2, IL-1H3, and IL-1H4. Like most other IL-1/FGFs, these proteins do not contain a hydrophobic leader sequence. IL-1H4 has a propeptide sequence, while IL-1H1, IL-1H2, and IL-1H3 encode only the mature protein. Circular dichroism spectra and thermal stability analysis suggest that 1H1 folds similarly to IL-1ra. The novel homologues are not widely expressed in mammals. IL-1H1 is constitutively expressed only in placenta and the squamous epithelium of the esophagus, However, IL-1H1 could be induced in vitro in keratinocytes by interferon-gamma and tumor necrosis factor-alpha and in vivo via a contact hypersensitivity reaction or herpes simplex virus infection. This suggests that IL-1H1 may be involved in pathogenesis of immune mediated disease processes. The addition of four novel IL-1 homologues suggests that the IL-1 family is significantly larger than previously thought.