Inflammatory prompts produce isoform‐specific changes in the expression of leukotriene B₄ ω‐hydroxylases in rat liver and kidney

Abstract

Cytochrome P450 (CYP) 4Fs metabolize leukotriene B 4 and other in£ammatory mediators in the arachidonic acid cascade. Here we show that lipopolysaccharide (LPS) treatment suppresses CYP4F4 and up-regulates CYP4F5 mRNA expression in rat liver whereas renal CYP4Fs are essentially unchanged. BaSO 4 treatment, in contrast, increases both hepatic and renal CYP4F expression levels. Thus, distinct regulatory mechanisms in CYP4F expression might operate under di¡erent in£ammatory prompts. To examine hepatic totipotency, primary hepatocytes were treated with varying doses of LPS resulting in decrease in all the CYP4F isoforms. Treatment of hepatocytes with 5 ng/ml of interleukin-1L L mimics the in vivo e¡ects of LPS on CYP4F expression. ß

Regulation of Cytochrome P450 4F11 by Nuclear Transcription Factor-κB

“…Overall, we believe that this regulation of CYP4F11 may be an important mechanism of compensation in cells. Most P450s are down-regulated during the inflammatory response, so it is unique that CYP4F11 is up-regulated (Morgan, 2001;Kalsotra et al, 2003;Morgan et al, 2008). For instance, CYP4F3A/B and CYP4F2 have been shown in our laboratory to be down-regulated during an inflammatory response (data not shown); thus, it may be beneficial to up-regulate CYP4F11 as a partial compensatory mechanism for activities of down-regulated isoforms.…”

Activation of the Acute Inflammatory Response Alters Cytochrome P450 Expression and Eicosanoid Metabolism

“…In contrast to the majority of P450s, hepatic CYP4A and CYP4F isoforms may be induced by inflammation, although this seems to be isoform-and species-specific (Sewer et al, 1996;Barclay et al, 1999;Kalsotra et al, 2003;Anwar-mohamed et al, 2010). The temporal profiles of hepatic Cyp4a12a, Cyp4a12b, and Cyp4f13 mRNA levels were similar to that for 20-HETE formation, which was also suppressed at 24 h, but to a lesser degree than EETϩDHET formation.…”

20-Hydroxylation is the CYP-dependent and retinoid-inducible leukotriene B4 inactivation pathway in human and mouse skin cells

“…Acute inflammation is a critical defense mechanism, but if not resolved sequelae due to chronic inflammation can be more injurious than the initial insult. We propose that induction of CYP4F enzymes may be a general mechanism how diverse epithelia influence the course of inflammation-driven disease and recovery from environmentally induced cell damage [3; 6; 33; 35; 36; 37; 38; 39]. Induction of these enzymes, for example by retinoids, may be exploited clinically to promote healing of inflamed, injured epithelial tissues.…”