固醇代谢失衡触发炎症小体：机制与原因。
Loss of sterol metabolic homeostasis triggers inflammasomes - how and why.
机构信息
Department of Biophysics and Biochemistry, University of California, San Francisco, CA 94158, USA.
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
出版信息
Curr Opin Immunol. 2019 Feb;56:1-9. doi: 10.1016/j.coi.2018.08.001. Epub 2018 Aug 29.
Proper regulation of sterol biosynthesis is critical for eukaryotic cellular homeostasis. Cholesterol and isoprenoids serve key roles in eukaryotic cells by regulating membrane fluidity and correct localization of proteins. It is becoming increasingly appreciated that dysregulated sterol metabolism engages pathways that lead to inflammation. Of particular importance are inflammasomes, which are multiplatform protein complexes that activate caspase-1 in order to process the pro-inflammatory and pyrogenic cytokines IL-1β and IL-18. In this review, we highlight recent research that links altered sterol biosynthetic pathway activity to inflammasome activation. We discuss how clues from human genetics have led to new insights into how alterations in isoprenoid biosynthesis connect to inflammation. We also discuss new mechanisms that show how macrophage cholesterol buildup can lead to inflammasome activation.
甾醇生物合成的适当调节对于真核细胞的内稳态至关重要。胆固醇和异戊二烯在真核细胞中通过调节膜流动性和蛋白质的正确定位来发挥关键作用。人们越来越认识到，失调的甾醇代谢会涉及到导致炎症的途径。特别重要的是炎性小体，它们是多平台蛋白复合物，可激活半胱天冬酶-1，以处理促炎和发热细胞因子 IL-1β 和 IL-18。在这篇综述中，我们强调了最近将改变的甾醇生物合成途径活性与炎性小体激活联系起来的研究。我们讨论了人类遗传学的线索如何导致人们对异戊二烯生物合成的改变如何与炎症相关有了新的认识。我们还讨论了显示巨噬细胞胆固醇积累如何导致炎性小体激活的新机制。
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