Injection of LPS causes transient suppression of biological clock genes in rats.
BACKGROUND
The biological clock regulates circadian rhythm and is important for sustaining homeostasis. Here we examined the response of biological clock genes to systemic inflammatory stimulation.


METHODS
At 08:00 h (= Zeitgeber time [ZT] 01), male Wistar rats (7-wk-old) maintained on a 12:12 h light:dark cycle (light on 07:00-19:00 h) received intravenous injection of 1 mg/kg lipopolysaccharide (LPS group) or 0.3 mL saline (control group). They were then sacrificed every 4 h (09:00 h = ZT 02, 13:00 h = ZT 06, 17:00 h = ZT 10, 21:00 h = ZT 14, 01:00 h = ZT 18, 05:00 h = ZT 22) over a 2-d period, and blood, brain, and liver samples were obtained for analysis (n = 4 at each time for each group). The expression levels of clock gene, rPer2, and those of clock controlled gene, rDBP, were quantified in the suprachiasmatic nucleus by in situ hybridization, while those of rPer1, rPer2, rDBP, rPPARA, and rFKBP51 in the liver were determined by quantitative RT-PCR.


RESULTS
In the suprachiasmatic nucleus of control rats, rPer2 and rDBP mRNA expression levels showed robust circadian patterns with peak levels at ZT 06 and ZT 10, respectively. LPS significantly suppressed both genes on day 1 but recovery was noted on day 2. Similarly, LPS significantly suppressed rPer1, rPer2, rDBP, rPPARA, and rFKBP51 mRNA expression levels in the liver on day 1 but recovery was noted on day 2, whereas a robust circadian pattern was noted in the control group.


CONCLUSIONS
Our results indicate that LPS causes transient suppression of the biological clock genes and suggest that the biological clock plays an important role in the response to systemic inflammatory stimulation.
Okada
Kazuyuki
K
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Yano
Masahiko
M
Doki
Yuichiro
Y
Azama
Takashi
T
Iwanaga
Hiroshi
H
Miki
Hirofumi
H
Nakayama
Mitsuo
M
Miyata
Hiroshi
H
Takiguchi
Shuji
S
Fujiwara
Yoshiyuki
Y
Yasuda
Takushi
T
Ishida
Norio
N
Monden
Morito
M
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects* / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006706:Homeostasis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D047493:PPAR alpha; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D022021:Tacrolimus Binding Proteins; D014157:Transcription Factors; D000099159:Tacrolimus Binding Protein 5; C485975:DBP protein, rat; C513311:Per2 protein, rat