Fuhlbrigge R C, Fine S M, Unanue E R, Chaplin D D
Department of Pathology, Washington University School of Medicine, Saint Louis, MO 63110.
Proc Natl Acad Sci U S A. 1988 Aug;85(15):5649-53. doi: 10.1073/pnas.85.15.5649.
Studies of interleukin 1 (IL-1) alpha and beta have emphasized their functional similarities. IL-1 alpha and -beta are encoded by ancestrally related genes that have diverged dramatically in primary sequence; however, only modest differences in the regulation or biological activity of IL-1 alpha and IL-1 beta have been documented. Here we show that mouse L cells transfected with murine pro-IL-1 alpha cDNA expressed biologically active, 33-kilodalton pro-IL-1 alpha, and that this pro molecule was neither processed to the 17-kilodalton mature form nor secreted. The transfected cells also expressed membrane-associated IL-1 biological activity, indicating that the pro-IL-1 alpha cDNA can direct expression of membrane-associated IL-1 and that cleavage of the pro molecule is not required for membrane presentation. In contrast, transfection of pro-IL-1 beta cDNA did not generate biologically active material in L cells. Evidence is presented that the native murine IL-1 beta precursor molecule is also biologically inactive in peritoneal exudate cells stimulated with lipopolysaccharide. These differences in distribution of the bioactive forms of IL-1 alpha and IL-1 beta may provide selective advantages for the maintenance of two gene products with similar functions.
白细胞介素1（IL-1）α和β的研究强调了它们的功能相似性。IL-1α和-β由在一级序列上有显著差异的祖先相关基因编码；然而，关于IL-1α和IL-1β在调节或生物学活性方面的差异仅有少量记录。我们在此表明，用鼠源前体IL-1α cDNA转染的小鼠L细胞表达具有生物活性的33千道尔顿前体IL-1α，且该前体分子既未被加工成17千道尔顿的成熟形式，也未被分泌。转染细胞还表达与膜相关的IL-1生物活性，这表明前体IL-1α cDNA可指导与膜相关的IL-1的表达，且前体分子的切割对于膜呈现并非必需。相比之下，前体IL-1β cDNA转染在L细胞中未产生具有生物活性的物质。有证据表明，天然鼠源IL-1β前体分子在用脂多糖刺激的腹膜渗出细胞中也无生物活性。IL-1α和IL-1β生物活性形式分布的这些差异可能为维持两种功能相似的基因产物提供了选择性优势。
