Differential effects of B- and T-lymphocyte mitogens on cytochrome P450 in mice

Lipopolysaccharide (LPS) is widely used as a B-lymphocyte mitogen and is known to depress expression of the cytochrome P450 (P450). However, there have been no studies regarding to the effects of the other mitogens on the expression of P450. This study investigated the effects of mitogens on the constitutive and inducible expression of mouse hepatic P450. Following treatment with B-lymphocyte mitogens, such as LPS and pokeweed mitogen (PWM), hepatic P450 content was reduced. LPS and PWM also suppressed activities of microsomal ethoxyresorufin O-deethylase, pentoxyresorufin O-dealkylase and aniline hydroxylase, a representative activity of P4501A1/2, P4502B1/2 and P4502E1, respectively, in both constitutive and P450 induced mice. However, there was no effect when treated with T-lymphocyte mitogens, such as concanavalin A and phytohemagglutinin. Suppression of P450 expression in the LPS- or PWM-treated mice occurred and was shown to involve a decrease in P450 protein and mRNA levels in liver. These results suggest that suppressive effects of mitogens on the expression of P450 might be different and that B-lymphocyte mitogens selectively depress the expression of P450.