title: Bacterial LPS differently modulates inflammasome gene expression and IL-1β secretion in trophoblast cells, decidual stromal cells, and decidual endothelial cells.
abstract: Three Nod-like receptors (NLR family, pyrin domain containing 1/NLRP1, NLR family, pyrin domain containing 3/NLRP3, NLR family, CARD domain containing 4/NLRC4) and the adaptor molecule PYD and CARD domain containing protein/PYCARD are involved in the assembling of multiprotein complexes known as inflammasomes, leading to caspase 1 activation and consequent interleukin (IL)-1β secretion. Considering that inflammasomes are involved in sensing pathogens and in triggering inflammatory and immune response, we hypothesized that they could also act in the placenta as an efficient innate mechanism during pregnancy infections. For this reason the activation of inflammasome was tested in 3 human placental cell populations in the presence of a common gram-negative compound (lipopolysaccharide [LPS]). The transcription of NLRP1, NLRP3, NLRC4, PYCARD, CASP1, and IL1B genes and the secretion of IL-1β were evaluated in human first trimester cytotrophoblasts (CTBs), decidual stromal cells (DSCs), and endothelial cells (DECs) stimulated with LPS. In CTBs and DSCs, LPS induced an augmented expression of CASP1 and IL1B and the specific upregulation of NLRP3 within the 3 NLRs tested. Moreover, LPS induced secretion of IL-1β from CTBs and DSCs. These results suggest the involvement of NLRP3 inflammasome in the placental innate response. The LPS did not affect inflammasome gene transcription and IL-1β production in DECs. Bacterial LPS enhances NLRP3 inflammasome components in trophoblast and DSCs, suggesting that this innate immune complex could play a key role in placental immune defense.
authors.affiliation: Laboratory of Medical Investigation in Dermatology and Immunodeficiency, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil. pontillo.a@gmail.com
authors.forename: A
authors.initials: A
authors.lastname: Pontillo
authors.forename: M
authors.initials: M
authors.lastname: Girardelli
authors.forename: C
authors.initials: C
authors.lastname: Agostinis
authors.forename: E
authors.initials: E
authors.lastname: Masat
authors.forename: R
authors.initials: R
authors.lastname: Bulla
authors.forename: S
authors.initials: S
authors.lastname: Crovella
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003656:Decidua / Q000187:drug effects* / Q000276:immunology; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D058847:Inflammasomes / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D014158:Transcription, Genetic; D014327:Trophoblasts / Q000187:drug effects* / Q000276:immunology
chemical_list: D002352:Carrier Proteins; D004731:Endotoxins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012333:RNA, Messenger; C044101:endotoxin, Escherichia coli