前沿：人类白细胞介素4受体α链Ile50Val变体在IgE合成中的主导作用。
Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis.
作者信息
Mitsuyasu H, Yanagihara Y, Mao X Q, Gao P S, Arinobu Y, Ihara K, Takabayashi A, Hara T, Enomoto T, Sasaki S, Kawai M, Hamasaki N, Shirakawa T, Hopkin J M, Izuhara K
机构信息
Department of Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
出版信息
J Immunol. 1999 Feb 1;162(3):1227-31.
Two variants of the IL-4R alpha-chain (IL-4Ralpha) gene have been recently identified in association with different atopic disorders. To clarify the etiological relationship between the two variants, we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Val or Ile at 50 and either Gln or Arg at 551. The substitution of Ile for Val augmented STAT6 activation, proliferation, and transcription activity of the Iepsilon promoter by IL-4, whereas that of Arg for Gln did not change these IL-4 signals. Arg551 was not associated with atopic asthma in the Japanese population. CD23 expression and IgE synthesis by IL-4 were augmented in Ile50-bearing PBMC, compared with those bearing Val50. Taken together, substitution of Arg551 does not enhance the IL-4 signal for generation of germline epsilon transcript, whereas the substitution of Ile50 contributes to enhancement of IgE synthesis.
最近发现白细胞介素-4受体α链（IL-4Rα）基因的两种变体与不同的特应性疾病相关。为了阐明这两种变体之间的病因关系，我们分析了携带第50位为缬氨酸（Val）或异亮氨酸（Ile）以及第551位为谷氨酰胺（Gln）或精氨酸（Arg）的四种IL-4Rα转染子对IL-4的反应性。用Ile替代Val增强了IL-4对STAT6的激活、增殖以及Iε启动子的转录活性，而用Arg替代Gln则未改变这些IL-4信号。在日本人群中，Arg551与特应性哮喘无关。与携带Val50的外周血单个核细胞（PBMC）相比，携带Ile50的PBMC中IL-4诱导的CD23表达和IgE合成增加。综上所述，Arg551的替代不会增强产生种系ε转录本的IL-4信号，而Ile50的替代有助于增强IgE合成。
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