Human cytomegalovirus infection induces leukotriene B4 and 5-lipoxygenase expression in human placentae and umbilical vein endothelial cells.

Abstract

INTRODUCTION:

Human cytomegalovirus (HCMV) can cause congenital infection with risk of neurological disability. Maternal-fetal transmission is associated with placental inflammation. 5-lipoxygenase (5-LO) is the key enzyme in the biosynthesis of Leukotrienes (LTs), which are proinflammatory mediators. This study investigated the effect of HCMV infection on 5-LO expression and Leukotriene-B4 (LTB4) induction in human placentae and umbilical vein endothelial cells (HUVEC).

METHODS:

Seven placentae from fetuses with congenital HCMV infection and brain damage and six controls were stained with HCMV-immediate-early-antigen (HCMV-IEA) and 5-LO by immunohistochemistry. 5-hydroxyeicosatetraenoic acid (5-HETE) and LTB4 were measured in culture supernatant from ex vivo HCMV-infected placental histocultures by liquid chromatography. In vitro, HCMV infected HUVEC cells were analyzed for 5-LO mRNA and protein expression by real time PCR and immunofluorescence staining.

RESULTS:

HCMV-IEA was abundant in all HCMV infected placentae but absent in control placentae. 5-LO expression was higher in endothelial and smooth muscle cells of HCMV-infected placentae, compared to control placentae. HCMV infection induced an up-regulation of LTB4 in ex vivo placental explants with higher levels of LTB4 at 72 h compared to controls (p = 0.002). In vitro, 5-LO transcript and protein expression were significantly induced in HCMV-infected HUVEC, compared to the control cultures (p = 0.036).

CONCLUSION:

The presence of HCMV coincided with high 5-LO expression in cells of in vivo HCMV infected placentae. HCMV induced up-regulation of 5-LO in both ex vivo HCMV-infected placental explants and HUVEC. HCMV induced LT-biosynthesis in congenitally infected placentae may have a role in pathogenesis of congenital HCMV disease.

• Authors: M Benard, K Straat, S Omarsdottir, K Leghmari, J Bertrand, C Davrinche, I Duga-Neulat, C Söderberg-Nauclér, A Rahbar, C Casper
• Journal: Placenta (Placenta) Vol. 35 Issue 6 Pg. 345-50 (Jun 2014) ISSN: 1532-3102 [Electronic] Netherlands
• PMID: 24746852 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Hydroxyeicosatetraenoic Acids
• RNA, Messenger
• Leukotriene B4
• 5-hydroxy-6,8,11,14-eicosatetraenoic acid
• Arachidonate 5-Lipoxygenase

Topics

• Arachidonate 5-Lipoxygenase (analysis, genetics)
• Cytomegalovirus Infections (congenital, enzymology, metabolism)
• Endothelial Cells (chemistry, enzymology)
• Female
• Human Umbilical Vein Endothelial Cells
• Humans
• Hydroxyeicosatetraenoic Acids (analysis)
• Immunohistochemistry
• Leukotriene B4 (analysis)
• Placenta (chemistry, enzymology)
• Pregnancy
• RNA, Messenger (analysis)
• Umbilical Veins (chemistry, enzymology)
• Up-Regulation