Interleukin 2 induction of cytochrome P450-linked monooxygenase systems of rat liver microsomes.
The effects of interleukin 2 (IL-2), a pivotal cytokine for generating an effective immune response, on rat liver microsomal cytochrome P450-linked monooxygenase systems were investigated by measuring the contents of cytochromes b5 and P450, and the activities of various xenobiotic-metabolizing enzymes [debrisoquine and bufuralol monooxygenases (CYP2D), 7-ethoxycoumarin O-deethylase, benzphetamine N-demethylase, aniline hydroxylase and p-nitroanisole N-demethylase]. The enzymatic activities except for p-nitroanisole N-demethylase and aniline hydroxylase were increased approximately to 1.3-fold of those of untreated liver microsomes following intraperitoneal injection of IL-2 (15 U/rat). However, the amount of immunoreactive b5 protein, and the activities of aniline hydroxylase and p-nitroanisole N-demethylase were not changed by injection of IL-2. To elucidate further the mechanism of the induction of CYP2D by IL-2, quantitative analyses of immunoreactive CYP2D protein and its mRNA were conducted by western blot and slot blot hybridization analyses. The results indicated that IL-2 induced an increase in the amounts of immunoreactive CYP2D protein and its mRNA. These enzymatic activities were thus up-regulated at the mRNA level.
Kurokohchi
K
K
Department of Biochemistry, Kagawa Medical School, Japan.
Matsuo
Y
Y
Yoneyama
H
H
Nishioka
M
M
Ichikawa
Y
Y
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000096:biosynthesis*; D015786:Cytochromes b5 / Q000032:analysis / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression; D007376:Interleukin-2 / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D015262:Xenobiotics / Q000494:pharmacology
D007376:Interleukin-2; D007527:Isoenzymes; D015262:Xenobiotics; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System