title: Effects of Lipopolysaccharide on Human First Trimester Villous Cytotrophoblast Cell Function In Vitro.
abstract: It has been shown that adverse obstetrical outcomes such as pre-eclampsia and intrauterine growth retardation correlate with maternal infection. In this study, we investigated mechanisms involved in infection-associated abnormalities in cytotrophoblast function. Primary human first trimester cytotrophoblast cells were isolated and treated with lipopolysaccharide (LPS). Levels of the cytokines and chemokines were measured and cytotrophoblast invasion was investigated. In addition, first trimester decidual macrophages were isolated and treated with the conditioned medium from LPS-treated cytotrophoblast cells, and macrophage migration was assessed. Coculturing decidual macrophages with cytotrophoblast cells was conducted to investigate macrophage costimulatory molecule and receptor expression and intracellular cytokine production. We found that LPS exposure increased cytotrophoblast production of pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, and chemokines IL-8, macrophage inflammatory protein (MIP)-1alpha, and CXCL12 in a dose-dependent manner. In addition, LPS decreased cytotrophoblast invasion, and its effect was Toll-like receptor 4 (TLR4)-dependent and partly TNF-alpha-dependent. Conditioned medium from LPS-stimulated cytotrophoblast cells increased decidual macrophage migration and this effect was partly TLR4-dependent. Furthermore, coculturing decidual macrophages with LPS-exposed cytotrophoblast cells up-regulated macrophage CD80 and CD86 expression and intracellular TNF-alpha and IL-12p40 production, while down-regulating macrophage CD206 and CD209 expression and intracellular IL-10 secretion. LPS-stimulated macrophages also inhibited cytotrophoblast invasion. In conclusion, our results indicate that LPS increases the production of a subset of proinflammatory cytokines and chemokines by human first trimester cytotrophoblast cells, decreases cytotrophoblast invasion, and alters the cross talk between cytotrophoblast cells and decidual macrophages.
authors.affiliation: Department of Obstetrics and Gynecology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China doctorlipingli@foxmail.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Jiaoqin
authors.initials: J
authors.lastname: Tu
authors.affiliation: Department of Obstetrics and Gynecology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, University of Missouri School of Medicine, Columbia, Missouri.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yabe
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, University of Missouri School of Medicine, Columbia, Missouri schustd@health.missouri.edu.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Schust
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
keywords: Toll-like receptor 4; cytotrophoblast; decidual macrophages; infection; lipopolysaccharide