Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus

Julie L Boles,1 Michael G Ross,1 Ron Beloosesky,2 Mina Desai,1 Louiza Belkacemi11Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute at Harbor-UCLA, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Torrance, CA...

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Autores principales:	Ross MG, Beloosesky R, Boles JL, Desai M, Belkacemi L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/04905c716d5449a6a152300b998fc6ac
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spelling	oai:doaj.org-article:04905c716d5449a6a152300b998fc6ac2021-12-02T01:10:34ZPlacental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus1178-7031https://doaj.org/article/04905c716d5449a6a152300b998fc6ac2012-07-01T00:00:00Zhttp://www.dovepress.com/placental-mediated-increased-cytokine-response-to-lipopolysaccharides--a10548https://doaj.org/toc/1178-7031Julie L Boles,1 Michael G Ross,1 Ron Beloosesky,2 Mina Desai,1 Louiza Belkacemi11Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute at Harbor-UCLA, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Torrance, CA, USA; 2Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, IsraelBackground: Cerebral palsy is a nonprogressive motor impairment syndrome that has no effective cure. The etiology of most cases of cerebral palsy remains unknown; however, recent epidemiologic data have demonstrated an association between fetal neurologic injury and infection/inflammation. Maternal infection/inflammation may be associated with the induction of placental cytokines that could result in increased fetal proinflammatory cytokine exposure, and development of neonatal neurologic injury. Therefore, we sought to explore the mechanism by which maternal infection may produce a placental inflammatory response. We specifically examined rat placental cytokine production and activation of the Toll-like receptor 4 (TLR4) pathway in response to lipopolysaccharide exposure at preterm and near-term gestational ages.Methods: Preterm (e16) or near-term (e20) placental explants from pregnant rats were treated with 0, 1, or 10 &micro;g/mL lipopolysaccharide. Explant integrity was assessed by lactate dehydrogenase assay. Interleukin-6 and tumor necrosis alpha levels were determined using enzyme-linked immunosorbent assay kits. TLR4 and phosphorylated nuclear factor kappa light chain enhancer of activated B cells (NF&kappa;B) protein expression levels were determined by Western blot analysis.Results: At both e16 and e20, lactate dehydrogenase levels were unchanged by treatment with lipopolysaccharide. After exposure to lipopolysaccharide, the release of interleukin-6 and tumor necrosis alpha from e16 placental explants increased by 4-fold and 8&ndash;9-fold, respectively (P &lt; 0.05 versus vehicle). Conversely, interleukin-6 release from e20 explants was not significantly different compared with vehicle, and tumor necrosis alpha release was only 2-fold higher (P &lt; 0.05 versus vehicle) following exposure to lipopolysaccharide. Phosphorylated NF&kappa;B protein expression was significantly increased in the nuclear fraction from placental explants exposed to lipopolysaccharide at both e16 and e20, although TLR4 protein expression was unaffected.Conclusion: Lipopolysaccharide induces higher interleukin-6 and tumor necrosis alpha expression at e16 versus e20, suggesting that preterm placentas may have a greater placental cytokine response to lipopolysaccharide infection. Furthermore, increased phosphorylated NF&kappa;B indicates that placental cytokine induction may occur by activation of the TLR4 pathway.Keywords: cytokines, lipopolysaccharide, NF&kappa;B, placenta, rat pregnancyRoss MGBeloosesky RBoles JLDesai MBelkacemi LDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2012, Iss default, Pp 67-75 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Ross MG Beloosesky R Boles JL Desai M Belkacemi L Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus
description	Julie L Boles,1 Michael G Ross,1 Ron Beloosesky,2 Mina Desai,1 Louiza Belkacemi11Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute at Harbor-UCLA, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Torrance, CA, USA; 2Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, IsraelBackground: Cerebral palsy is a nonprogressive motor impairment syndrome that has no effective cure. The etiology of most cases of cerebral palsy remains unknown; however, recent epidemiologic data have demonstrated an association between fetal neurologic injury and infection/inflammation. Maternal infection/inflammation may be associated with the induction of placental cytokines that could result in increased fetal proinflammatory cytokine exposure, and development of neonatal neurologic injury. Therefore, we sought to explore the mechanism by which maternal infection may produce a placental inflammatory response. We specifically examined rat placental cytokine production and activation of the Toll-like receptor 4 (TLR4) pathway in response to lipopolysaccharide exposure at preterm and near-term gestational ages.Methods: Preterm (e16) or near-term (e20) placental explants from pregnant rats were treated with 0, 1, or 10 &micro;g/mL lipopolysaccharide. Explant integrity was assessed by lactate dehydrogenase assay. Interleukin-6 and tumor necrosis alpha levels were determined using enzyme-linked immunosorbent assay kits. TLR4 and phosphorylated nuclear factor kappa light chain enhancer of activated B cells (NF&kappa;B) protein expression levels were determined by Western blot analysis.Results: At both e16 and e20, lactate dehydrogenase levels were unchanged by treatment with lipopolysaccharide. After exposure to lipopolysaccharide, the release of interleukin-6 and tumor necrosis alpha from e16 placental explants increased by 4-fold and 8&ndash;9-fold, respectively (P &lt; 0.05 versus vehicle). Conversely, interleukin-6 release from e20 explants was not significantly different compared with vehicle, and tumor necrosis alpha release was only 2-fold higher (P &lt; 0.05 versus vehicle) following exposure to lipopolysaccharide. Phosphorylated NF&kappa;B protein expression was significantly increased in the nuclear fraction from placental explants exposed to lipopolysaccharide at both e16 and e20, although TLR4 protein expression was unaffected.Conclusion: Lipopolysaccharide induces higher interleukin-6 and tumor necrosis alpha expression at e16 versus e20, suggesting that preterm placentas may have a greater placental cytokine response to lipopolysaccharide infection. Furthermore, increased phosphorylated NF&kappa;B indicates that placental cytokine induction may occur by activation of the TLR4 pathway.Keywords: cytokines, lipopolysaccharide, NF&kappa;B, placenta, rat pregnancy
format	article
author	Ross MG Beloosesky R Boles JL Desai M Belkacemi L
author_facet	Ross MG Beloosesky R Boles JL Desai M Belkacemi L
author_sort	Ross MG
title	Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus
title_short	Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus
title_full	Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus
title_fullStr	Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus
title_full_unstemmed	Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus
title_sort	placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/04905c716d5449a6a152300b998fc6ac
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Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus

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