title: A role for PKCzeta in the LPS-induced translocation NF-kappaB p65 subunit in cultured myometrial cells.
abstract: Human myometrial cells respond to the endotoxin lipopolysaccharide (LPS) by activation of protein kinase C (PKC) zeta and nuclear translocation of the p65 subunit of NF-kB. Our first objective was to determine the expression of TLR4 in cultured myometrial cells. Positive immunoreactivity observed for TLR4 suggests that myometrial cells have the potential to respond to LPS. To confirm that LPS signals via TLR4, the ability of an anti-TLR4 neutralizing antibody to block LPS-induced translocation of p65 was demonstrated. To determine whether LPS-induced nuclear translocation of p65 is mediated through the PKC pathway, myometrial cells were treated with various inhibitors of the PKC isoforms already characterized in human myometrium. Neither the selective conventional PKC inhibitor nor the inhibitor of PKCdelta affected NF-kB activation. By contrast, we found that treatment of myometrial cells with an antisense against PKCzeta affect LPS-induced nuclear translocation of the p65 subunit of NF-kB. Accordingly, our data support the notion that PKCzeta is essential for LPS-induced NF-kB p65 subunit nuclear translocation in human myometrial cells.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Inserm U427, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, 4, avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Dallot
authors.forename: Céline
authors.initials: C
authors.lastname: Méhats
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Oger
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Leroy
authors.forename: Michelle
authors.initials: M
authors.lastname: Breuiller-Fouché
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D009215:Myometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D051996:Transcription Factor RelA; D000099221:Protein Kinase C zeta
chemical_list: D007527:Isoenzymes; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011493:Protein Kinase C; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D051996:Transcription Factor RelA; D000099221:Protein Kinase C zeta; C495345:TLR4 protein, human