Intra-uterine Growth Restriction Downregulates the Hepatic Toll Like Receptor-4 Expression and Function
Maternal starvation is a significant cause of intrauterine growth restriction (IUGR) in the world and increases the risk of infection in the neonate. We examined the effect of maternal starvation on Toll like receptor (TLR)4 expression in hepatic, splenic and i...
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doaj-12c03b97fbab453aba96f22731c7ee8b2020-11-24T23:02:16ZengHindawi LimitedClinical and Developmental Immunology1740-25221740-25302005-01-01121596610.1080/17402520400008905Intra-uterine Growth Restriction Downregulates the Hepatic Toll Like Receptor-4 Expression and FunctionOzlem Equils0Sapna Singh1Semra Karaburun2Daning Lu3Manikkavasagar Thamotharan4Sherin U. Devaskar5Department of Pediatrics, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center David Geffen School of Medicine at UCLA, Los Angeles, CA 90048, USAPennsylvania State University Jefferson Medical College, Philadelphia 19107, USADepartment of Pediatrics, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center David Geffen School of Medicine at UCLA, Los Angeles, CA 90048, USADepartment of Pediatrics, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center David Geffen School of Medicine at UCLA, Los Angeles, CA 90048, USADepartment of Pediatrics, David Geffen School of Medicine at UCLA and Mattel Children's Hospital at UCLA, Los Angeles, CA 90024, USADepartment of Pediatrics, David Geffen School of Medicine at UCLA and Mattel Children's Hospital at UCLA, Los Angeles, CA 90024, USAMaternal starvation is a significant cause of intrauterine growth restriction (IUGR) in the world and increases the risk of infection in the neonate. We examined the effect of maternal starvation on Toll like receptor (TLR)4 expression in hepatic, splenic and intestinal tissues obtained from the adult IUGR offspring of prenatal calorie restricted rats. The hepatic TLR4 protein concentration was undetectable in the IUGR rats that had restricted milk intake during the suckling period (SM/SP; n = 4, p < 0.05) as compared to the normal growth controls (CM/CP; n=4), and access to ad lib milk intake during the sucking period partially corrected the hepatic TLR4 expression (SM/CP; n = 4). IUGR had no effect on the splenic (n = 4) or intestinal (n = 4) TLR4 mRNA levels. In the liver, IUGR led to a 20% increase in baseline tumor necrosis factor (TNF)-α mRNA expression ( p < 0.03) and a 70% increase in interleukin-1β (IL-1β) mRNA expression ( p < 0.008) as compared to the control rats (CM/CP; n = 7). LPS-induced hepatic TNF-α release was significantly higher in SM/SP as compared to CM/CP. We propose that IUGR dysregulates TLR4 expression and function in the offspring, which may help explain the increased risk of Gram-negative sepsis and inflammatory diseases in this population.http://dx.doi.org/10.1080/17402520400008905 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ozlem Equils Sapna Singh Semra Karaburun Daning Lu Manikkavasagar Thamotharan Sherin U. Devaskar |
spellingShingle |
Ozlem Equils Sapna Singh Semra Karaburun Daning Lu Manikkavasagar Thamotharan Sherin U. Devaskar Intra-uterine Growth Restriction Downregulates the Hepatic Toll Like Receptor-4 Expression and Function Clinical and Developmental Immunology |
author_facet |
Ozlem Equils Sapna Singh Semra Karaburun Daning Lu Manikkavasagar Thamotharan Sherin U. Devaskar |
author_sort |
Ozlem Equils |
title |
Intra-uterine Growth Restriction Downregulates the Hepatic Toll Like Receptor-4 Expression and Function |
title_short |
Intra-uterine Growth Restriction Downregulates the Hepatic Toll Like Receptor-4 Expression and Function |
title_full |
Intra-uterine Growth Restriction Downregulates the Hepatic Toll Like Receptor-4 Expression and Function |
title_fullStr |
Intra-uterine Growth Restriction Downregulates the Hepatic Toll Like Receptor-4 Expression and Function |
title_full_unstemmed |
Intra-uterine Growth Restriction Downregulates the Hepatic Toll Like Receptor-4 Expression and Function |
title_sort |
intra-uterine growth restriction downregulates the hepatic toll like receptor-4 expression and function |
publisher |
Hindawi Limited |
series |
Clinical and Developmental Immunology |
issn |
1740-2522 1740-2530 |
publishDate |
2005-01-01 |
description |
Maternal starvation is a significant cause of intrauterine growth restriction
(IUGR) in the world and increases the risk of infection in the neonate. We examined
the effect of maternal starvation on Toll like receptor (TLR)4 expression in hepatic,
splenic and intestinal tissues obtained from the adult IUGR offspring of prenatal
calorie restricted rats. The hepatic TLR4 protein concentration was undetectable in
the IUGR rats that had restricted milk intake during the suckling period
(SM/SP; n = 4, p < 0.05) as compared to the normal
growth controls (CM/CP; n=4),
and access to ad lib milk intake during the sucking period partially corrected the
hepatic TLR4 expression (SM/CP; n = 4). IUGR had no effect
on the splenic (n = 4) or
intestinal (n = 4) TLR4 mRNA levels. In the liver, IUGR
led to a 20% increase in
baseline tumor necrosis factor (TNF)-α mRNA expression ( p < 0.03) and a 70%
increase in interleukin-1β (IL-1β) mRNA expression ( p < 0.008) as compared to
the control rats (CM/CP; n = 7). LPS-induced hepatic
TNF-α release was significantly
higher in SM/SP as compared to CM/CP. We propose that IUGR dysregulates
TLR4 expression and function in the offspring, which may help explain
the increased risk of Gram-negative sepsis and inflammatory diseases in this
population. |
url |
http://dx.doi.org/10.1080/17402520400008905 |
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