Froy Oren, Chapnik Nava, Miskin Ruth
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality, The Hebrew University of Jerusalem, Rehovot, Israel.
FASEB J. 2005 Nov;19(13):1920-2. doi: 10.1096/fj.05-4216fje. Epub 2005 Aug 29.
The innate immunity utilizes a plethora of antibacterial polypeptides, known as defensins, to combat ingested bacteria. Mouse enteric defensins (cryptdins) are produced and secreted constitutively but are overexpressed in instances of infection and/or inflammation. Our objective was to determine whether the biological clock plays a role in cryptdin expression under healthy conditions. Analysis of cryptdin 1 and cryptdin 4 expression in the ileum and jejunum of the small intestine of FVB/N mice around the circadian cycle revealed oscillation that peaked at the end of the dark phase. To eliminate the possibility that cryptdin oscillation stems from food intake, we analyzed cryptdin expression under fasting conditions and found oscillation but with a 3 h phase-shift. Comparison of cryptdin expression in two mouse strains (C57BL/6 vs. FVB/N) revealed higher levels in C57BL/6, a mouse strain that is highly susceptible to enteric infection, due, most likely, to impaired cryptdin maturation. The results of this study indicate the involvement of the biological clock in regulating cryptdin expression in the small intestine and reinforce the capacity of food to act as a zeitgeber (synchronizer). With the assumption of similar control in humans, our results may imply that defensin expression peaks during the day.
先天性免疫利用大量抗菌多肽（即防御素）来对抗摄入的细菌。小鼠肠道防御素（隐窝素）持续产生和分泌，但在感染和/或炎症情况下会过度表达。我们的目标是确定生物钟在健康条件下是否对隐窝素表达起作用。对FVB/N小鼠小肠回肠和空肠中隐窝素1和隐窝素4在昼夜周期中的表达分析显示，其表达呈振荡变化，在黑暗期结束时达到峰值。为排除隐窝素振荡源于食物摄入的可能性，我们分析了禁食条件下隐窝素的表达，发现仍有振荡，但相位偏移了3小时。对两种小鼠品系（C57BL/6与FVB/N）中隐窝素表达的比较显示，C57BL/6小鼠品系中的隐窝素水平更高，该品系对肠道感染高度敏感，这很可能是由于隐窝素成熟受损所致。本研究结果表明生物钟参与调节小肠中隐窝素的表达，并强化了食物作为授时因子（同步器）的作用。假设人类存在类似的调控机制，我们的结果可能意味着防御素表达在白天达到峰值。
