LPS induces secretion of chemokines by human syncytiotrophoblast cells in a MAPK-dependent manner

Abstract The maintenance of pregnancy depends on the nature and magnitude of the immune responses induced within the placenta. An elevated proinflammatory response in the intervillous space (IVS) is associated with adverse pregnancy outcomes. It is becoming more apparent that the syncytiotrophoblast...

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Bibliographic Details
Published in:Journal of reproductive immunology 2007-02, Vol.73 (1), p.20-27
Main Authors: Lucchi, Naomi W, Moore, Julie M
Format: Article
Language:English
Subjects:
Biological and medical sciences
Chemokine CCL3
Chemokine CCL4
Chemokines - genetics
Chemokines - metabolism
Embryology: invertebrates and vertebrates. Teratology
Female
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Humans
IL-8
Intercellular Adhesion Molecule-1 - metabolism
Interleukin-8 - genetics
Interleukin-8 - immunology
Lipopolysaccharide
Lipopolysaccharides - immunology
Lipopolysaccharides - pharmacology
Macrophage Inflammatory Proteins - genetics
Macrophage Inflammatory Proteins - immunology
MAPK
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - metabolism
Mitogen-Activated Protein Kinases - metabolism
Obstetrics and Gynecology
Phosphorylation
Placenta
Placenta - cytology
Placenta - immunology
Pregnancy - immunology
Syncytiotrophoblast
Trophoblasts - drug effects
Trophoblasts - immunology
Up-Regulation
β chemokines
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Summary:Abstract The maintenance of pregnancy depends on the nature and magnitude of the immune responses induced within the placenta. An elevated proinflammatory response in the intervillous space (IVS) is associated with adverse pregnancy outcomes. It is becoming more apparent that the syncytiotrophoblast (ST) cells, which are in direct contact with maternal blood, are capable of contributing to the local immune environment in response to maternal hematogenous infections or exposure to proinflammatory stimuli. In this study, we investigated mechanisms by which ST might recruit maternal immune effectors to the IVS in response to bacterial infections. To assess this, primary trophoblasts were isolated from fresh term placentas and stimulated with lipopolysaccharide (LPS). LPS induced time-dependent expression and secretion of IL-8, macrophage inflammatory protein (MIP)-1α and MIP-1β from ST cells and an upregulation of ICAM-1. The stimulation also resulted in the activation of ERK1/2 mitogen-activated protein kinase (MAPK) but not p38 or JNK1/2. Inhibition of ERK1/2 lead to a reduction in the secretion of MIP-1β and IL-8 suggesting that their production is at least partly dependent on ERK1/2 activation. Results from this study reveal a potential mechanism by which differentiated ST cells modulate the local maternal immune responses during an intrauterine bacterial infection. Such responses could contribute to the clearance of the infection but also pathological features observed in intrauterine infections of the placenta.
ISSN:0165-0378
1872-7603
DOI:10.1016/j.jri.2006.05.005