Expression of cytochromes P450 4F4 and 4F5 in infection and injury models of inflammation

X. Cui, A. Kalsotra, A. M. Robida, D. Matzilevich, A. N. Moore, C. L. Boehme, E. T. Morgan, P. K. Dash, H. W. Strobel

Research output: Contribution to journalArticlepeer-review

Abstract

Lipopolysaccharide (LPS) treatment of rats suppresses CYP 4F4 and 4F5 expression by 50 and 40%, respectively, in a direct fashion occurring in the liver. This contention is borne out by essentially parallel dose-dependent changes observed upon treatment of rat hepatocyte cultures with LPS. An alternate avenue of triggering the inflammatory cascade is traumatic brain injury by controlled cortical impact. Such injury brings about a dramatic change in the expression of CYP 4F4 and 4F5 mRNA which reaches its greatest effect 24 h after impact compared with sham-operated but uninjured controls. At time points after 24 h the expression of both isoforms increases dramatically reaching highest levels at 2 weeks post-injury. These changes in mRNA expression are mirrored by changes in protein expression. The results are consistent with the notion that immediately after injury concentrations of leukotriene and prostaglandin mediators are elevated by decreased CYP 4F concentrations. As time after injury increases those conditions reverse. Increased CYP 4F expression leads to diminished concentrations of leukotriene and prostaglandin mediators and then to recovery and repair.

Original languageEnglish (US)
Pages (from-to)325-331
Number of pages7
JournalBiochimica et Biophysica Acta - General Subjects
Volume1619
Issue number3
DOIs
StatePublished - Feb 17 2003
Externally publishedYes

Keywords

  • Brain cytochrome P450 distribution
  • CYP 4F subfamily expression
  • CYP 4F subfamily suppression by inflammation
  • Inflammation and P450 expression
  • Lipopolysaccharide and CYP 4F subfamily expression
  • Regulation of CYP 4F expression

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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