Regulation of antimicrobial peptide gene expression by nutrients and by-products of microbial metabolism.
Regulation of antimicrobial peptide gene expression by nutrients and by-products of microbial metabolism.
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DOI：
10.1007/s00394-012-0415-4
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发表时间：
2012-12
影响因子：
5
通讯作者：
Gombart AF
中科院分区：
文献类型：
--
作者：
Campbell Y;Fantacone ML;Gombart AF
抗菌肽 (AMP) 由不断暴露于环境微生物的免疫细胞和上皮细胞合成和分泌。 AMP 对于屏障防御至关重要，缺乏会导致感染的易感性增加。除了破坏细菌、病毒和真菌膜完整性的能力外，AMP 还能结合脂多糖，充当免疫细胞的趋化剂，与细胞受体结合并调节细胞因子和趋化因子的表达。这些额外的生物活性可以解释 AMP 在炎症性疾病和癌症中的作用。调节 AMP 的内源表达为感染和疾病提供了潜在的治疗方法。本综述审查了已发表的体外和体内研究数据，这些研究报告了营养物质和微生物代谢副产物对抗菌肽基因表达的影响，以强调人们对膳食化合物在调节先天免疫反应中的作用的新认识。维生素 A 和 D、膳食组蛋白脱乙酰酶和肠道微生物代谢的副产物（丁酸和次级胆汁酸）已被发现可以调节人类 AMP 的表达。维生素 D 缺乏与感染易感性增加相关，补充研究表明维生素 D 可以改善感染防御能力。使用丁酸盐进行的动物和人类临床研究表明，增加结肠中 AMP 的表达可以防止感染。这些发现表明饮食和/或食用营养补充剂可用于改善和/或调节免疫功能。此外，肠道微生物代谢的副产物对于与肠上皮细胞和免疫细胞的通讯可能很重要，从而影响 AMP 的表达。这种相互作用可能有助于建立粘膜屏障，以防止共生微生物或病原微生物入侵肠上皮。
Antimicrobial peptides (AMPs) are synthesized and secreted by immune and epithelial cells that are constantly exposed to environmental microbes. AMPs are essential for barrier defense, and deficiencies lead to increased susceptibility to infection. In addition to their ability to disrupt the integrity of bacterial, viral and fungal membranes, AMPs bind lipopolysaccharides, act as chemoattractants for immune cells and bind to cellular receptors and modulate the expression of cytokines and chemokines. These additional biological activities may explain the role of AMPs in inflammatory diseases and cancer. Modulating the endogenous expression of AMPs offers potential therapeutic treatments for infection and disease. The present review examines the published data from both in vitro and in vivo studies reporting the effects of nutrients and by-products of microbial metabolism on the expression of antimicrobial peptide genes in order to highlight an emerging appreciation for the role of dietary compounds in modulating the innate immune response. Vitamins A and D, dietary histone deacetylases and by-products of intestinal microbial metabolism (butyrate and secondary bile acids) have been found to regulate the expression of AMPs in humans. Vitamin D deficiency correlates with increased susceptibility to infection, and supplementation studies indicate an improvement in defense against infection. Animal and human clinical studies with butyrate indicate that increasing expression of AMPs in the colon protects against infection. These findings suggest that diet and/or consumption of nutritional supplements may be used to improve and/or modulate immune function. In addition, by-products of gut microbe metabolism could be important for communicating with intestinal epithelial and immune cells, thus affecting the expression of AMPs. This interaction may help establish a mucosal barrier to prevent invasion of the intestinal epithelium by either mutualistic or pathogenic microorganisms.
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影响因子：
3.1
作者：
Gombart AF
通讯作者：
Gombart AF
影响因子：
3.7
作者：
Hertting, Olof;Holm, Asa;Brauner, Annelie
通讯作者：
Brauner, Annelie
影响因子：
4.8
作者：
Gombart, AF;Borregaard, N;Koeffler, HP
通讯作者：
Koeffler, HP
影响因子：
4.8
作者：
Harder, J;Bartels, J;Schröder, JM
通讯作者：
Schröder, JM
影响因子：
32.4
作者：
Hall JA;Grainger JR;Spencer SP;Belkaid Y
通讯作者：
Belkaid Y