Expression of cytochrome P450 4A mRNA in mouse lung: effect of clofibrate and interleukin-1beta.

Abstract

Cytochromes P450 4A (CYP4A) metabolize arachidonic acid into hydroxyeicosatetraenoic acids (HETEs) that exhibit potent actions on airway smooth muscle tone. In the lung, modifications in CYP4A expression and HETEs production could thus contribute to alterations in airway reactivity. We characterized expression of CYP4A in the lung of BALB/c mice, and studied its regulation by the CYP4A inducer, clofibrate and by the pro-inflammatory and asthma-associated cytokine, interleukin-1beta (IL-1beta). Messenger RNA (mRNA) expression of Cyp4a10, 4a12 and 4a14 was assessed in lung from control and clofibrate or IL-1beta-treated mice using polymerase chain reaction after reverse transcription of total lung RNA. Cyp4a12 mRNA was the only Cyp4a mRNA detected in lung tissue from control mice, as well as mice treated with clofibrate or IL-1beta. In contrast, mRNA of all isoforms were found at significant levels in liver from control mice and at increased levels in liver from clofibrate-treated animals. Lung levels of Cyp4a12 mRNA were enhanced by ninefold in mice treated with clofibrate and by fourfold in animals injected with IL-1beta. In conclusion, Cyp4a12, but not Cyp4a10 or Cyp4a14, is expressed in the lung of BALB/c mice, and may be upregulated by clofibrate or IL-1beta. Since IL-1beta has been largely associated with asthma, our data suggest that CYP4A expression could be altered in asthmatic conditions and may thus contribute to changes in airway reactivity.