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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Altered hepatic inflammatory response in the offspring following prenatal LPS exposure
Oliver Surriga1, Andres Ortega, Viren Jadeja
1Department of Biological Sciences, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA.
Insights
Maternal immune activation during pregnancy reduced the hepatic inflammatory response in offspring. Specifically, it diminished interleukin-6 (IL-6) expression and attenuated p42/44 MAPK phosphorylation following LPS stimulation.
Area of Science:
- Immunology
- Developmental Biology
- Toxicology
Background:
- Maternal immune activation (MIA) during pregnancy impacts offspring immune development.
- The liver's inflammatory response in offspring is a critical area of study for understanding MIA effects.
Purpose of the Study:
- To investigate the effects of MIA on the hepatic inflammatory response in offspring.
- To analyze the expression of toll-like receptor 4 (TLR-4) pathway components and cytokines in offspring livers.
Main Methods:
- Pregnant rats were treated with lipopolysaccharide (LPS) or saline.
- Offspring were stimulated with LPS or saline at postnatal day 21.
- Hepatic expression of TLR-4, CD14, TNF-alpha, IL-1 beta, IL-6, and MAPK pathway activation (p38 MAPK, p42/44 MAPK) was assessed.
Main Results:
- MIA significantly diminished LPS-induced IL-6 mRNA expression in offspring liver.
- MIA attenuated LPS-induced p42/44 MAPK phosphorylation in offspring liver.
- No significant effect of MIA on p38 MAPK phosphorylation was observed.
Conclusions:
- MIA can differentially modulate hepatic inflammatory mediators in offspring.
- p42/44 MAPK signaling may play a role in regulating hepatic IL-6 expression following MIA.
- These findings highlight the long-term immune programming effects of prenatal inflammation.
Abstract:
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.
