title: Internalization of Staphylococcus aureus by bovine endothelial cells is associated with the activity state of NF-kappaB and modulated by the pro-inflammatory cytokines TNF-alpha and IL-1beta.
abstract: Bacterial internalization is an important process in the pathogenesis of infectious diseases in which nuclear factor kappaB (NF-kappaB) plays a prominent role. We present pharmacological evidence indicating that in bovine endothelial cells (BEC) the internalization of Staphylococcus aureus, a pathogenic bacterium that causes mastitis in bovine cattle, was associated with the activation of NF-kappaB. The internalization of S. aureus increased when BEC were stimulated with alpha-tumour necrosis factor (TNF-alpha) or beta-interleukin 1 (IL-1beta) which are known activators of NF-kappaB. SN50 (an inhibitor peptide of NF-kappaB nuclear translocation) and BAY 11-7083 (a chemical that inhibits the IkappaBalpha phosphorylation) caused significant reduction in S. aureus intracellular number, indicating that its internalization was associated with the NF-kappaB activity. Furthermore, specific inhibition of c-Jun N-terminal kinase with SP600125 (SP) or p-38 with SB203580 (SB) did not cause any change in the S. aureus intracellular number compared with the untreated control. Finally, TNF-alpha treatment of BEC after the addition of both SP and SB, induced a significant increase in S. aureus internalization above the control value. These data indicate that NF-kappaB activity is associated with S. aureus internalization and suggest that this transcription factor may play a role in the pathophysiology of bovine mastitis caused by this bacterium.
authors.affiliation: Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Michoacán, México.
authors.forename: J
authors.initials: J
authors.lastname: Oviedo-Boyso
authors.forename: J G
authors.initials: JG
authors.lastname: Barriga-Rivera
authors.forename: J J
authors.initials: JJ
authors.lastname: Valdez-Alarcón
authors.forename: A
authors.initials: A
authors.lastname: Bravo-Patiño
authors.forename: A
authors.initials: A
authors.lastname: Cárabez-Trejo
authors.forename: M
authors.initials: M
authors.lastname: Cajero-Juárez
authors.forename: V M
authors.initials: VM
authors.lastname: Baizabal-Aguirre
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002417:Cattle; D015169:Colony Count, Microbial; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007093:Imidazoles; D053583:Interleukin-1beta / Q000276:immunology* / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology; D008414:Mastitis, Bovine / Q000276:immunology / Q000382:microbiology*; D008854:Microscopy, Electron / Q000662:veterinary; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology*; D009570:Nitriles / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011725:Pyridines; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D013211:Staphylococcus aureus / Q000276:immunology*; D013450:Sulfones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000873:Anthracenes; C416282:BAY 11-7085; D004791:Enzyme Inhibitors; D007093:Imidazoles; D053583:Interleukin-1beta; D016328:NF-kappa B; D009570:Nitriles; D010455:Peptides; D011725:Pyridines; C118258:SN50 peptide; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; C093642:SB 203580