Effects of interleukin 1 alpha on the activities and gene expressions of the cytochrome P450IID subfamily.
The mechanism by which recombinant human interleukin 1 alpha (rhIL-1 alpha) inhibits the activities of drug-metabolizing enzymes of rat liver microsomes, especially debrisoquine monooxygenase and bufuralol monooxygenase (both cytochrome P450IID supported reactions), as well as other enzymes, was investigated by injecting IL-1 alpha into rats. rhIL-1 alpha suppressed the activities of various P450-linked monooxygenase systems such as aminopyrine N-demethylase, benzphetamine N-demethylase, and 7-ethoxycoumarin O-deethylase. It also suppressed the activities of debrisoquine monooxygenase and bufuralol monooxygenase. On the other hand, IL-1 alpha had little effect on the activity of p-nitroanisole N-demethylase. The suppression of debrisoquine monooxygenase and bufuralol monooxygenase activities was caused by a decrease in the amounts of immunoreactive P450IID protein and its mRNA. The reduction rates in the level of immunoreactive P450IID protein and its mRNA were comparable. These results suggest that at the mRNA level, the enzymatic activities of debrisoquine monooxygenase and bufuralol monooxygenase are down-regulated by IL-1 alpha.
Kurokohchi
K
K
Department of Biochemistry, Kagawa Medical School, Japan.
Yoneyama
H
H
Matsuo
Y
Y
Nishioka
M
M
Ichikawa
Y
Y
D015660:7-Alkoxycoumarin O-Dealkylase / Q000037:antagonists & inhibitors; D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System; D015660:7-Alkoxycoumarin O-Dealkylase; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; D000633:Aminopyrine N-Demethylase