title: Inflammatory responses in embryonal cardiomyocytes exposed to LPS challenge: an in vitro model of deciphering the effects of LPS on the heart.
abstract: This study is focused on the links between the major products of inflammation and cell damage induced by the administration of lipopolysaccharide (LPS) from Salmonella typhimurium in embryonal cardiomyocytes. LPS treatment for 72 hours induced transcription factor NF-kappaB activation, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression, nitric oxide (NO) and tumor necrosis factor (TNF)-alpha release. Moreover, LPS administration induced a significant cell loss, reversed by the NO-synthases inhibitor, suggesting a relationship between cell damage and iNOS-dependent NO overproduction. Cell death was reversed by the specific NF-kappaB inhibitor, TPCK, whereas COX-2 specific inhibitor determined an increase of cell damage in terms of apoptosis, as observed by YO-PRO immunostaining, DNA laddering analysis and caspase-3 activation. Overall these findings evidenced a selective role for NF-kappaB in mediating NO-induced cell damage and a protective action by COX-2 in LPS-treated embryonal cardiomyocytes. The reflection of these experiments on human cardiac pathology will be discussed.
authors.affiliation: Department of Human Anatomy and Histology, University of Bari, Pzza G Cesare, 11 I-70124 Bari, Italy. ma.panaro@anatomia.uniba.it
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Panaro
authors.forename: Angela
authors.initials: A
authors.lastname: Acquafredda
authors.forename: Pasqua
authors.initials: P
authors.lastname: Cavallo
authors.forename: Antonia
authors.initials: A
authors.lastname: Cianciulli
authors.forename: Concetta
authors.initials: C
authors.lastname: Saponaro
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mitolo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000196:embryology*; D066298:In Vitro Techniques; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D014108:Tosylphenylalanyl Chloromethyl Ketone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D053148:Caspase 3