School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
J Biol Chem. 2013 Aug 9;288(32):22893-8. doi: 10.1074/jbc.R113.486464. Epub 2013 Jun 24.
The interplay between immunity, inflammation, and metabolic changes is a growing field of research. Toll-like receptors and NOD-like receptors are families of innate immune receptors, and their role in the human immune response is well documented. Exciting new evidence is emerging with regard to their role in the regulation of metabolism and the activation of inflammatory pathways during the progression of metabolic disorders such as type 2 diabetes and atherosclerosis. The proinflammatory cytokine IL-1β appears to play a central role in these disorders. There is also evidence that metabolites such as NAD(+) (acting via deacetylases such as SIRT1 and SIRT2) and succinate (which regulates hypoxia-inducible factor 1α) are signals that regulate innate immunity. In addition, the extracellular overproduction of metabolites such as uric acid and cholesterol crystals acts as a signal sensed by NLRP3, leading to the production of IL-1β. These observations cast new light on the role of metabolism during host defense and inflammation.
免疫、炎症和代谢变化之间的相互作用是一个日益发展的研究领域。 Toll 样受体和 NOD 样受体是先天免疫受体家族，它们在人类免疫反应中的作用已得到充分证实。令人兴奋的新证据表明，它们在代谢紊乱（如 2 型糖尿病和动脉粥样硬化）进展过程中调节代谢和激活炎症途径方面发挥作用。促炎细胞因子 IL-1β 似乎在这些疾病中起着核心作用。也有证据表明，代谢物如 NAD+（通过去乙酰化酶如 SIRT1 和 SIRT2 发挥作用）和琥珀酸（调节缺氧诱导因子 1α）是调节先天免疫的信号。此外，尿酸和胆固醇晶体等代谢物的细胞外过度产生充当被 NLRP3 感知的信号，导致 IL-1β 的产生。这些观察结果为代谢在宿主防御和炎症中的作用提供了新的视角。
