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Catalytic characterization and cytokine mediated regulation of cytochrome P450 4Fs in rat hepatocytes.


ABSTRACT: Cytochrome P450 (CYP) 4F mediated leukotriene B(4) (LTB(4)) metabolism modulates inflammation during injury and infection. Here we show that in addition to LTB(4), the recombinant rat CYP4Fs catalyze omega-hydroxylations of lipoxin A(4), and hydroxyeicosatetraeonic acids. CYP4F gene regulation studies in primary hepatocytes reveal that pro-inflammatory cytokines interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF) -alpha produce a general inductive response whereas IL-10, an anti-inflammatory cytokine, suppresses CYP4F expression. The molecular mechanism behind IL-6 related induction of CYP4F4 and 4F5 is partially signal transducer and activator of transcription 3 (STAT3) dependent. When hepatocytes are subjected to high concentrations of LTB(4) or prostaglandin E(2), lipid mediat

SUBMITTER: Kalsotra A 

PROVIDER: S-EPMC2574503 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature