Mouse intestinal cryptdins exhibit circadian oscillation.
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.
Froy
Oren
O
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality, The Hebrew University of Jerusalem, Rehovot, Israel. froy@agri.huji.ac.il
Chapnik
Nava
N
Miskin
Ruth
R
D000818:Animals; D001683:Biological Clocks; D015152:Blotting, Northern; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm; D023082:Defensins / Q000737:chemistry; D005260:Female; D007082:Ileum / Q000378:metabolism; D007249:Inflammation; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000096:biosynthesis; D009991:Oscillometry; D056950:Period Circadian Proteins; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013997:Time Factors; D023084:alpha-Defensins / Q000096:biosynthesis
D018797:Cell Cycle Proteins; D023082:Defensins; D009687:Nuclear Proteins; C539022:PER1 protein, human; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D011498:Protein Precursors; D023084:alpha-Defensins; C401847:cryptdin 4, mouse; C059569:cryptdin