在缺氧后，雄性和发情前期雌性小鼠的库普弗细胞中，髓样分化因子88（MyD88）和Src的表达受到不同的调控。
MyD88 and Src are differentially regulated in Kupffer cells of males and proestrus females following hypoxia.
作者信息
Zheng Rui, Pan George, Thobe Bjoern M, Choudhry Mashkoor A, Matsutani Takeshi, Samy T S Anantha, Kang Shih-Ching, Bland Kirby I, Chaudry Irshad H
机构信息
Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, AL 35294-0019, USA.
出版信息
Mol Med. 2006 Apr-Jun;12(4-6):65-73. doi: 10.2119/2006-00030.Zheng.
Abstract
Hypoxia produces sex dimorphic immune responses in males and proestrus females. Because Kupffer cells are the major source of proinflammatory cytokines, studies were conducted to discern IL-6 production in mouse Kupffer cells following hypoxia. Hypoxia enhances TLR4 expression in Kupffer cells irrespective of sex. However, MyD88 and Src expression in Kupffer cells decreased significantly after hypoxia in proestrus females, whereas Src protein expression and phosphorylation increased in males in concurrence with differences in IL-6 production. 17beta-estradiol administration elevated MyD88 and Src expression in males to levels in normoxic proestrus females. Administration of Src inhibitor in hypoxic males prevented increased IL-6 production. Thus, differential regulation of MyD88 and Src in males and females plays an important role in sex-specific immune response following hypoxia.
摘要
缺氧会在雄性和发情前期雌性中产生性别二态性免疫反应。由于库普弗细胞是促炎细胞因子的主要来源，因此开展了相关研究以辨别缺氧后小鼠库普弗细胞中白细胞介素-6（IL-6）的产生情况。无论性别如何，缺氧都会增强库普弗细胞中Toll样受体4（TLR4）的表达。然而，发情前期雌性小鼠缺氧后，库普弗细胞中的髓样分化因子88（MyD88）和Src表达显著降低，而雄性小鼠中Src蛋白表达和磷酸化增加，同时IL-6产生存在差异。给予17β-雌二醇可将雄性小鼠中的MyD88和Src表达提高到正常氧分压下发情前期雌性小鼠的水平。在缺氧雄性小鼠中给予Src抑制剂可阻止IL-6产生增加。因此，雄性和雌性中MyD88和Src的差异调节在缺氧后的性别特异性免疫反应中起重要作用。
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本文引用的文献
1
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J Endotoxin Res. 2005;11(5):311-20. doi: 10.1179/096805105X58733.
2
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Biochem Pharmacol. 2005 Oct 15;70(8):1231-40. doi: 10.1016/j.bcp.2005.07.020.
3
Src family kinase inhibitor PP1 reduces secondary damage after spinal cord compression in rats.
J Neurotrauma. 2004 Jul;21(7):923-31. doi: 10.1089/0897715041526230.
4
Src-family kinases: rheostats of immune cell signaling.Src家族激酶：免疫细胞信号传导的变阻器
Mol Immunol. 2004 Jul;41(6-7):631-43. doi: 10.1016/j.molimm.2004.04.010.
5
Osmotic regulation of cell function and possible clinical applications.细胞功能的渗透调节及可能的临床应用。
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6
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Infect Immun. 2004 Apr;72(4):2123-30. doi: 10.1128/IAI.72.4.2123-2130.2004.
7
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8
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9
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10
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J Leukoc Biol. 2003 Oct;74(4):479-85. doi: 10.1189/jlb.0203082. Epub 2003 Jul 1.
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