Arjona Alvaro, Sarkar Dipak K
Endocrine Program and Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
J Interferon Cytokine Res. 2006 Sep;26(9):645-9. doi: 10.1089/jir.2006.26.645.
Circadian and daily rhythms regulate many aspects of physiology and behavior. Although a growing number of studies suggest that circadian disruptions may render organisms more susceptible to infection and cancer, the molecular links between the circadian system and the immune system are largely unknown. Here we report that mice carrying a loss-of-function mutation in the Per2 gene, a key component of the molecular circadian clock, lacked the physiologic daily rhythm of interferon-gamma (IFN-gamma) mRNA and protein expression in the spleen. These observations were associated with a significant alteration in the expression of canonical clock genes. In addition, Per2 mutant mice failed to show a daily rhythm in IFN-gamma serum levels, which were significantly lower than those determined in wild-type mice during the early light period. These findings provide novel evidence for a direct circadian regulation of IFN-gamma, a critical cytokine modulating the immune response.
昼夜节律和每日节律调节着生理和行为的许多方面。尽管越来越多的研究表明，昼夜节律紊乱可能使生物体更容易受到感染和患癌症，但昼夜节律系统与免疫系统之间的分子联系在很大程度上仍不清楚。在此我们报告，携带分子生物钟关键成分Per2基因功能缺失突变的小鼠，脾脏中干扰素-γ（IFN-γ）mRNA和蛋白质表达缺乏生理性的每日节律。这些观察结果与经典生物钟基因表达的显著改变有关。此外，Per2突变小鼠的IFN-γ血清水平未显示出每日节律，在光照早期其水平显著低于野生型小鼠。这些发现为IFN-γ的直接昼夜节律调节提供了新证据，IFN-γ是一种调节免疫反应的关键细胞因子。
