title: Human trophoblast responses to Porphyromonas gingivalis infection.
abstract: Porphyromonas gingivalis is a periodontal pathogen that is also associated with preterm low-birthweight delivery. We investigated the transcriptional responses of human extravillous trophoblasts (HTR-8) to infection with P. gingivalis. Over 2000 genes were differentially regulated in HTR-8 cells by P. gingivalis. In ontology analyses of regulated genes, overpopulated biological pathways included mitogen-activated protein (MAP) kinase signaling and cytokine production. Immunoblots confirmed overexpression of the MAP kinase pathway components MEK3, p38 and Max. Furthermore, P. gingivalis infection induced phosphorylation and activation of MEK3 and p38. Increased production of interleukin (IL)-1beta and IL-8 by HTR-8 cells was demonstrated phenotypically by enzyme-linked immunosorbent assay of HTR-8 cell lysates and culture supernatants. Hence, infection of trophoblasts by P. gingivalis can impact signal transduction pathways and modulate cytokine expression, outcomes that could disrupt the maintenance of pregnancy.
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Riewe
authors.forename: J J
authors.initials: JJ
authors.lastname: Mans
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: J
authors.initials: J
authors.lastname: Katz
authors.forename: K T
authors.initials: KT
authors.lastname: Shiverick
authors.forename: T A
authors.initials: TA
authors.lastname: Brown
authors.forename: R J
authors.initials: RJ
authors.lastname: Lamont
mesh_terms: D016866:Bacteroidaceae Infections / Q000150:complications*; D050976:Basic-Leucine Zipper Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D048371:MAP Kinase Kinase 3 / Q000096:biosynthesis / Q000235:genetics; D020935:MAP Kinase Signaling System; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology / Q000382:microbiology*; D015533:Transcriptional Activation; D014327:Trophoblasts / Q000378:metabolism / Q000382:microbiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D053583:Interleukin-1beta; D016209:Interleukin-8; D007378:Interleukins; C067850:Myc associated factor X; D048051:p38 Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3