Title

Proteasome Inhibition Augments Cigarette Smoke-Induced GM-CSF Expression in Trophoblast Cells via the Epidermal Growth Factor Receptor

Authors

Authors

Y. Y. Fu; J. C. Nergard; N. K. Barnette; Y. L. Wang; K. X. Chai;L. M. Chen

Comments

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Abbreviated Journal Title

PLoS One

Keywords

COLONY-STIMULATING FACTOR; NF-KAPPA-B; MATERNAL SMOKING; TOBACCO USE; PREECLAMPSIA; PREGNANCY; WOMEN; ACTIVATION; PLACENTA; MICE; Multidisciplinary Sciences

Abstract

Maternal cigarette smoking has adverse effects on pregnancy outcomes. The granulocyte-macrophage colony-stimulating factor (GM-CSF) is an essential cytokine for a normal pregnancy. We investigated the impact of cigarette smoke extract (CSE) on GM-CSF expression in human cytotrophoblast cells and suggested a cellular mechanism underlying the CSE-induced GM-CSF expression. An immortalized normal human trophoblast cell line (B6Tert-1) was treated with CSE. The viability and proliferation of the CSE-treated B6Tert-1 cells were evaluated, and the expression of GM-CSF in these cells was quantified at the mRNA and the protein levels by means of reverse-transcription and quantitative polymerase chain reaction (RT-qPCR); and enzyme-linked immunosorbent assay (ELISA), respectively. Human trophoblast cells treated with CSE had an increased expression of GM-CSF at both the mRNA and the protein levels. The CSE-induced GM-CSF expression was synergistically enhanced by the addition of the proteasome inhibitor MG-132, but inhibited by AG-1478, an inhibitor of the epidermal growth factor receptor (EGFR) kinase. Furthermore, CSE treatment increased the phosphorylation of the extracellular-signal regulated kinases (ERK1/2) in the trophoblast cells. The expression of other growth factors such as heparin-binding epidermal growth factor-like growth factor (HB-EGF) and vascular endothelial growth factor (VEGF) was also evaluated. Our data suggested that cigarette smoking and proteasome inhibition synergistically up-regulate GM-CSF cytokine expression by activating the EGFR signaling pathway.

Journal Title

Plos One

Volume

7

Issue/Number

8

Publication Date

1-1-2014

Document Type

Article

Language

English

First Page

9

WOS Identifier

WOS:000308063700033

ISSN

1932-6203

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