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IRAK-4在白介素-1受体/Toll样受体(IL-1R/TLRs)介导的炎症信号通路中的关键作用

李帆 芮耀诚

李帆, 芮耀诚. IRAK-4在白介素-1受体/Toll样受体(IL-1R/TLRs)介导的炎症信号通路中的关键作用[J]. 药学实践与服务, 2011, 29(1): 1-3,14.
引用本文: 李帆, 芮耀诚. IRAK-4在白介素-1受体/Toll样受体(IL-1R/TLRs)介导的炎症信号通路中的关键作用[J]. 药学实践与服务, 2011, 29(1): 1-3,14.
LI Fan, RUI Yao-Cheng. The key function of IRAK-4 in the inflammation signal pathway mediated by Toll-like receptors[J]. Journal of Pharmaceutical Practice and Service, 2011, 29(1): 1-3,14.
Citation: LI Fan, RUI Yao-Cheng. The key function of IRAK-4 in the inflammation signal pathway mediated by Toll-like receptors[J]. Journal of Pharmaceutical Practice and Service, 2011, 29(1): 1-3,14.

IRAK-4在白介素-1受体/Toll样受体(IL-1R/TLRs)介导的炎症信号通路中的关键作用

The key function of IRAK-4 in the inflammation signal pathway mediated by Toll-like receptors

  • 摘要: 白介素-1受体相关激酶4(interleukin-1 receptor-associated kinase 4;IRAK-4)是近年来发现的参与机体先天性免疫反应过程中的关键分子。它与另外3个成员IRAK-1、IRAK-2、IRAK-M同属于IRAK家族,目前经过对IRAK-4分子的激酶活性以及其对炎症反应的正向和负向的调控作用的研究表明,IRAK-4分子联系着上下游的信号转导,在TLRs/IL-1R介导的炎症信号通路中的作用更为关键。本文就IRAK-4分子的活性、以及IRAK-4分子在TLRs/IL-1R介导的炎症信号转导通路中的作用作一综述。以期设计出针对IRAK-4特异性的药物,或者通过基因治疗手段干预IRAK-4表达,为感染控制提供新的思路,开发出新的抗炎药物。
  • [1] Rekhter M, Staschke K, Estridge T, et al. Genetic ablation of IRAK-4 kinase activity inhibits vascular lesion formation[J]. Biochem Biophys Res Commun, 2008, 367(3):642.
    [2] Kim TW, Staschke K, Bulek K, et al. A critical role for IRAK4 kinase activity in Toll-like receptor-mediated innate immunity[J]. The Journal of Experimental Medicine, 2007, 204(5):1025.
    [3] Lye E, Mirtsos C, Suzuki M, et al. The role of interleukin 1 receptor-associated kinase-4 (IRAK-4) kinase activity in IRAK-4-mediated signaling[J]. The Journal of Biological Chemistry, 2004, 279(39):40653.
    [4] Qin JZ, Jiang ZF, Qian YC, et al. IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness[J]. The Journal of Biological Chemistry, 2004, 279(25):26748.
    [5] Song KW, Talamas FX, Suttmann RT, et al. The kinase activities of interleukin-1 receptor associated kinase (IRAK)-1 and 4 are redundant in the control of inflammatory cytokine expression in human cells[J]. Molecular Immunology, 2009,46:1458.
    [6] Hatao F, Yamamoto M, Muroi M, et al. MyD88-induced downregulation of IRAK-4 and its structural requirements[J]. FEMS Immunol Med Microbial, 2008, 53:260.
    [7] Hatao F, Muroi M, Hiki N, et al. Prolonged Toll-like receptor stimulation leads to down-regulation of IRAK-4 protein[J]. Leukoc.Biol, 2004, 76:904.
    [8] Suzuki N, Suzuki S,Yeh WC, et al. IRAK-4 as the central TIR signaling mediator in innate immunity[J]. Trends in Immunology, 2002, 23(10):503.
    [9] Cheng H, Addona T, Keshishian H, et al. Regulation of IRAK-4 kinase activity via autophosphorylation within its activation loop[J]. Biochemical and Biophysical Research Communications, 2007, 352:609.
    [10] Kuglstatter A, Villasen AG, Shaw D, et al. Cutting Edge: IL-1 receptor-associated kinase 4 structures reveal novel features and multiple conformations[J]. The Journal of Immunology, 2007, 178:2641.
    [11] Lasker MV, Gajjar MM, Nair SK,et al. Cutting Edge: Molecular structure of the IL-1R-associated kinase-4 death domain and its implications for TLR signaling[J]. The Journal of Immunology, 2005, 175:4175.
    [12] Suzuki N, Suzuki S, Millar DG, et al. A critical role for the innate immune signaling molecule IRAK-4 in T cell activation[J]. Science, 2006, 311(5769):1927.
    [13] Chandrasekar B, Mummidid S, Valente AJ, et al. The pro-atherogenic cytokine interleukin-18 induces CXCL16 expression in rat aortic smooth muscle cells via MyD88, interleukin-1 receptor associated kinase, tumor necrosis factor receptor associated factor 6, c-Src, phosphatidylinositol 3 kinase, Akt, c-Jun N- terminal kinase, and activator protein-1 signaling[J]. J Biol Chem, 2005, 280(28):26263.
    [14] Pacquelet S, Johnson JL, Ellis BA, et al. Cross-talk between IRAK-4 and the NADPH oxidase[J]. Biochem. J, 2007, 403:451.
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  • 收稿日期:  2010-09-20
  • 修回日期:  2010-10-21

IRAK-4在白介素-1受体/Toll样受体(IL-1R/TLRs)介导的炎症信号通路中的关键作用

摘要: 白介素-1受体相关激酶4(interleukin-1 receptor-associated kinase 4;IRAK-4)是近年来发现的参与机体先天性免疫反应过程中的关键分子。它与另外3个成员IRAK-1、IRAK-2、IRAK-M同属于IRAK家族,目前经过对IRAK-4分子的激酶活性以及其对炎症反应的正向和负向的调控作用的研究表明,IRAK-4分子联系着上下游的信号转导,在TLRs/IL-1R介导的炎症信号通路中的作用更为关键。本文就IRAK-4分子的活性、以及IRAK-4分子在TLRs/IL-1R介导的炎症信号转导通路中的作用作一综述。以期设计出针对IRAK-4特异性的药物,或者通过基因治疗手段干预IRAK-4表达,为感染控制提供新的思路,开发出新的抗炎药物。

English Abstract

李帆, 芮耀诚. IRAK-4在白介素-1受体/Toll样受体(IL-1R/TLRs)介导的炎症信号通路中的关键作用[J]. 药学实践与服务, 2011, 29(1): 1-3,14.
引用本文: 李帆, 芮耀诚. IRAK-4在白介素-1受体/Toll样受体(IL-1R/TLRs)介导的炎症信号通路中的关键作用[J]. 药学实践与服务, 2011, 29(1): 1-3,14.
LI Fan, RUI Yao-Cheng. The key function of IRAK-4 in the inflammation signal pathway mediated by Toll-like receptors[J]. Journal of Pharmaceutical Practice and Service, 2011, 29(1): 1-3,14.
Citation: LI Fan, RUI Yao-Cheng. The key function of IRAK-4 in the inflammation signal pathway mediated by Toll-like receptors[J]. Journal of Pharmaceutical Practice and Service, 2011, 29(1): 1-3,14.
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