Maternally-administered lipopolysaccharide (LPS) increases tumor necrosis factor alpha in fetal liver and fetal brain: its suppression by low-dose LPS pretreatment.
Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including intra-uterine fetal death (IUFD), intra-uterine growth retardation (IUGR) and neurological injury. In the LPS model, tumor necrosis factor alpha (TNF-alpha) is the major mediator leading to IUFD, IUGR and neurological injury. In the present study, we investigated the effect of maternally-administered LPS on TNF-alpha in maternal serum, amniotic fluid, fetal liver and fetal brain. The timed pregnant mice were intraperitoneally (i.p.) injected with a single dose of LPS (500microg/kg) on gestational day 17. As expected, TNF-alpha was obviously increased in maternal serum and amniotic fluid in response to LPS. Although maternally-administered LPS also increased the level of TNF-alpha protein in fetal liver and brain, no significant difference in TNF-alpha mRNA level in fetal liver and brain was observed among different groups, suggesting that the increased TNF-alpha protein in fetal liver and brain may be transferred from either the maternal circulation or amniotic fluid or placenta. When the pregnant mice were pretreated with a low-dose LPS (10microg/kg, i.p.) at 4, 12, 24 or 48h before LPS (500microg/kg, i.p.), LPS-evoked TNF-alpha in maternal serum and amniotic fluid was significantly inhibited. Importantly, low-dose LPS pretreatment also greatly attenuated LPS-induced increases in TNF-alpha protein in fetal liver and fetal brain. Taken together, these results indicate that perinatal exposure to low-dose LPS induces a reduced sensitivity to subsequent LPS challenge.
Department of Toxicology, Anhui Medical University, Hefei 230032, PR China.
Huan
H
Ning
Hua
H
Wang
Lei
L
Zhao
Cheng
C
Zhang
Xiang-Yun
XY
Li
Yuan-Hua
YH
Chen
De-Xiang
DX
Xu
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008813:Mice, Inbred ICR; D010920:Placenta / Q000378:metabolism; D021041:Placental Circulation; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics / Q000378:metabolism*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha