RESUMO
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 microg/kg LPS or saline on day 18 of pregnancy, subsequently stimulated the offspring with 250 microg/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)-alpha, interleukin (IL)-1 beta, 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.
Assuntos
Hepatite/imunologia , Imunidade Materno-Adquirida/imunologia , Lipopolissacarídeos/imunologia , Fígado/imunologia , Animais , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Interleucina-6/imunologia , Interleucina-6/metabolismo , Receptores de Lipopolissacarídeos/imunologia , Receptores de Lipopolissacarídeos/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/imunologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/imunologia , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
To investigate the effects of maternal infection on the offspring's inflammatory response, pups born to LPS- or saline-treated dams were stimulated with LPS or saline, and the expression of cytokines and chemokines was examined. We found that at P21, pups born to LPS-treated dams exhibited diminished serum levels of TNF-alpha, IL-1beta, and IL-6, and inhibited mRNA levels of cytokines, including TNF-alpha, IL-1beta, and IL-6, and chemokines, including MIP-1beta, MIP-2, and KC, in the brain, as compared to pups born to saline-treated dams at 2 h following LPS stimulation. Our results suggest that maternal infection suppresses the offspring's inflammatory response to LPS.
