LPS induces secretion of chemokines by human syncytiotrophoblast cells in a MAPK-dependent manner.
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)-1alpha and MIP-1beta 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-1beta 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.
Lucchi
Naomi W
NW
Department of Infectious Diseases, College of Veterinary Medicine and Center for Tropical and Emerging Global Diseases, University of Georgia, 500 DW Brooks Dr. Athens, GA, USA.
Moore
Julie M
JM
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010920:Placenta / Q000166:cytology / Q000276:immunology; D011247:Pregnancy / Q000276:immunology*; D014327:Trophoblasts / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D016209:Interleukin-8; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D018799:Intercellular Adhesion Molecule-1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases