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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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Citing This Article：

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).