title: Chlamydophila pneumoniae induces ICAM-1 expression in human aortic endothelial cells via protein kinase C-dependent activation of nuclear factor-kappaB.
abstract: Chlamydophila pneumoniae has an epidemiological link with atherosclerosis and acute cardiovascular events. One mechanism that may explain such a link is the increased expression of intracellular adhesion molecule-1 (ICAM-1) in C pneumoniae-infected endothelial cells. Upregulation of ICAM-1 by C pneumoniae is well recognized and has been extensively studied, but the signaling pathways involved are not yet defined. Because upregulation of ICAM-1 by cytokines and other stimuli has been shown to be mediated by either mitogen-activated protein kinase, protein kinase C (PKC), or nuclear factor-kappaB (NF-kappaB) pathways, we examined whether these pathways were involved in the ICAM-1 upregulation induced by C pneumoniae. Our data show a time-dependent phosphorylation of p44/p42 and SAPK/JNK pathways in C pneumoniae-infected cells. However, inhibition of the classic mitogen-activated protein kinase pathway using the PD98059 and U0126 inhibitors and inhibition of SAPK/JNK pathway did not suppress C pneumoniae-induced ICAM-1 expression. C pneumoniae also activates the NF-kappaB pathway at 30 minutes after infection. Treatment of human aortic endothelial cells (HAECs) with the NF-kappaB inhibitors BAY117085 and caffeic acid phenethyl ester led to a concentration-dependent inhibition of C pneumoniae-induced ICAM-1 upregulation. Finally, C pneumoniae-infected HAECs show membrane translocation of total PKC 30 minutes after cell infection. Calphostin C, a general PKC inhibitor, blocked both C pneumoniae-induced ICAM-1 expression and C pneumoniae-induced NF-kappaB translocation. In conclusion, we demonstrated that C pneumoniae-induced ICAM-1 expression in HAECs requires NF-kappaB and PKC activation and that NF-kappaB activation is PKC dependent.
authors.affiliation: Department of Microbiology and Immunology, Ralph H. Johnson VA Medical Center and Medical University of South Carolina, Strom Thurmond Research Building, 114 Doughty St, Charleston, SC 29425, USA. virellam@musc.edu
authors.forename: Silvana A
authors.initials: SA
authors.lastname: Vielma
authors.forename: Gregor
authors.initials: G
authors.lastname: Krings
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents; D001011:Aorta / Q000166:cytology; D002109:Caffeic Acids / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000378:metabolism / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013450:Sulfones; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; C416282:BAY 11-7085; D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D009570:Nitriles; D012333:RNA, Messenger; D013450:Sulfones; D018799:Intercellular Adhesion Molecule-1; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol