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不同功能位点介导#alpha#干扰素的免疫调节和中枢镇痛作用

王云霞, 蒋春雷, 宋连霞, 路长林, 邵小燕, 由振东, 黄爱军, 崔瑞耀, 刘新垣

第二军医大学神经生物学教研室、神经科学研究所.上海 200433；青岛医学院病理生理学教研室.山东,青岛 266021；中科院上海生物化学研究所.上海 200031

摘要

细胞因子#alpha#干扰素(IFN#alpha#)具有中枢镇痛作用。抗内源性阿片肽血清与IFN#alpha#能发生明显的交叉反应,提示IFN#alpha#与内源性阿片肽之间存在着共同的抗原决定基。采用基因定点突变技术,获得系列IFN#alpha#突变体,并分别测定其免疫学活性和镇痛能力。结果显示,IFN#alpha#突变体Y129S-IFN#alpha#免疫学活性显著下降,但仍然保留了很强的镇痛能力,阿片受体拮抗剂纳洛酮能够阻断Y129S-IFN#alpha#的镇痛作用。实验结果表明,IFN#alpha#分子存在着相互独立的免疫和镇痛两个功能位点,分别介导免疫调节作用和中枢镇痛作用。

Distinct structural bases of the immunoregulatory and central analgesic effects of IFN#alpha#

Wang Yunxia, Jiang Chunlei, Song Lianxia, Lu Changlin, Shao Xiaoyan, You Zhendong, Huang Aijun, Cui Ruiyao, Liu Xinyuan

Department of Neurobiology,Second Military Medical University.Shanghai 200433；China；Shanghai Institute of Biochemistry,Chinese Academy of Sciences.Shanghai 200031

Abstract

Interferon-alpha (IFN#alpha#), a cytokine, is also an analgesic molecule. There is significant cross reactivity between IFN#alpha# and anti-opioid sera, suggesting a strong antigenic relatedness between human IFN#alpha# molecules and opioid peptides. Different structural basis of the immunoactivity and analgesic effect of IFN#alpha# can be demonstrated by different reactivities of the two reactions towards different mutants of IFN#alpha# obtained by using the site-directed mutagenesis. When the 129th Tyr residue of human IFN#alpha# was mutated to Ser, the immunoactivity of the mutant almost disappeared, while the strong analgesic activity still persisted, which could be blocked by naloxone. These results indicate that there exist distinct domains in the IFN#alpha# molecule, which mediate immune and analgesic effects differentially, and that the receptor mechanism underlying immune and analgesic effects of IFN#alpha# may be different.

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王云霞, 蒋春雷, 宋连霞, 路长林, 邵小燕, 由振东, 黄爱军, 崔瑞耀, 刘新垣. 不同功能位点介导#alpha#干扰素的免疫调节和中枢镇痛作用[J]. 生理学报 2000; 52 (3): .

Wang Yunxia, Jiang Chunlei, Song Lianxia, Lu Changlin, Shao Xiaoyan, You Zhendong, Huang Aijun, Cui Ruiyao, Liu Xinyuan. Distinct structural bases of the immunoregulatory and central analgesic effects of IFN#alpha#. Acta Physiol Sin 2000; 52 (3): (in Chinese with English abstract).