Altered hepatic inflammatory response in the offspring following prenatal LPS exposure

There is increasing evidence that maternal immune activation has a significant impact on the offspring's immune function. In this study, we examined the effects of maternal immune activation on the offspring's hepatic inflammatory response. We treated pregnant rats with 500 μg/kg LPS or saline on day 18 of pregnancy, subsequently stimulated the offspring with 250 μg/kg LPS or saline at postnatal day (P) 21, and then examined the expression of LPS cell surface receptors, namely toll-like receptor (TLR)-4 and CD14, and cytokines, namely tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, as well as the activation of key intracellular mediators of the TLR-4 signaling cascade, namely p38 MAPK and p42/44 MAPK, in the offspring liver. We found that LPS-induced mRNA expression of IL-6 in the pups born to LPS-treated dams was significantly diminished compared with that in the pups born to saline-treated dams. Furthermore, maternal immune activation attenuated LPS-induced phosphorylation of p42/44 MAPK compared with the control pups without significantly affecting the phosphorylation of p38 MAPK. The correlation between the level of IL-6 expression and that of phosphorylated p42/44 MAPK suggests that p42/44 MAPK may play an important role in regulating hepatic IL-6 expression. Our results also suggest that maternal immune activation could have differential effects on various inflammatory mediators in the liver of the offspring.