Injection of LPS causes transient suppression of biological clock genes in rats

J Surg Res. 2008 Mar;145(1):5-12. doi: 10.1016/j.jss.2007.01.010.

Abstract

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.

Materials and 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.

Conclusion: 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.

MeSH terms

  • Animals
  • Biological Clocks / drug effects*
  • Biological Clocks / genetics*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / drug effects*
  • Homeostasis / genetics
  • Lipopolysaccharides / pharmacology*
  • Liver / metabolism
  • Male
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Period Circadian Proteins
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Suprachiasmatic Nucleus / metabolism
  • Tacrolimus Binding Proteins / genetics
  • Tacrolimus Binding Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Cell Cycle Proteins
  • DBP protein, rat
  • DNA-Binding Proteins
  • Lipopolysaccharides
  • Nuclear Proteins
  • PPAR alpha
  • Per2 protein, rat
  • Period Circadian Proteins
  • RNA, Messenger
  • Transcription Factors
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5