Inflammatory stimuli, such as bacterial LPS, alter the expression of many
cytochromes P450.
CYP2C and CYP2J subfamily members actively metabolize
fatty acids to bioactive
eicosanoids, which exhibit potent anti-inflammatory effects. Herein, we examined
mRNA levels of the 15 mouse
Cyp2c and 7 mouse Cyp2j
isoforms in liver, kidney, duodenum, and brain over a 96-h time course of LPS-induced
inflammation and resolution. Plasma and liver
eicosanoid levels were also measured by liquid chromatography with tandem mass spectrometry. Expression changes in
Cyp2c and Cyp2j
isoforms were both
isoform and tissue specific. Total liver
Cyp2c and Cyp2j
mRNA content was reduced by 80% 24 h after LPS but recovered to baseline levels by 96 h. Total
Cyp2c and Cyp2j
mRNA in kidney (-19%) and duodenum (-64%) were reduced 24 h after LPS but recovered above baseline by 72 h. Total
Cyp2c and Cyp2j
mRNA content in brain was elevated at all time points after LPS dosing. Plasma
eicosanoids transiently increased 3-6 h after administration of LPS. In liver, esterified
oxylipin levels decreased during acute
inflammation and before recovering. The biphasic suppression and recovery of mouse
Cyp2c and Cyp2j
isoforms and associated changes in
eicosanoid levels during LPS-induced
inflammation and resolution may have important physiologic consequences.-Graves, J. P., Bradbury, J. A., Gruzdev, A., Li, H., Duval, C., Lih, F. B., Edin, M. L., Zeldin, D. C. Expression of
Cyp2c/Cyp2j subfamily members and
oxylipin levels during LPS-induced
inflammation and resolution in mice.