title: Bacterial induction of early response genes and activation of proapoptotic factors in pleural mesothelial cells.
abstract: In bacterial empyema the pleural mesothelium is constantly exposed to microorganisms. Staphylococcus aureus (S. aureus) is one of the most frequent pathogens associated with empyema. In an earlier study we demonstrated that S. aureus induced barrier dysfunction in pleural mesothelial cell monolayers. In the present study we report that S. aureus activates the early response genes c-fos and c-jun and activator protein-1 (AP-1), and induces proapoptosis genes Bad and Bak in primary mouse pleural mesothelial cells (PMCs). Our data indicate that in PMCs S. aureus induces apoptosis in a time- and multiplicity of infection (MOI)-dependent manner. Staphylococcus aureus induced Bcl (2), Bcl-X (L), c-fos, c-jun, and AP-1 expression in PMCs during the initial phase of infection. In S. aureus-infected PMCs, Bad and Bak gene expression was increased and correlated with DNA fragmentation and cytochrome-c release. Bcl (2) and Bcl-X (L) gene expression was significantly lower in S. aureus-infected PMCs than in uninfected PMCs 12 h postinfection. We conclude that at the initial stage of infection S. aureus modulates expression of early response genes c-fos and c-jun, and in the late phase of infection S. aureus induces expression of proapoptotic genes Bak and Bad in PMCs. Silencing AP-1 significantly inhibited S. aureus-induced Bak and Bad expression in PMCs. The upregulation of early response genes during the early phase of infection may contribute to the activation of proapoptotic genes Bak and Bad and release of cytochrome-c, caspase-3 thereby resulting in apoptosis in PMCs.
authors.affiliation: Department of Medicine, College of Medicine, University of Florida, JHMHC, P.O. Box 100225, Gainesville, Florida, 32610-0225, USA. mkamal@medicine.ufl.edu
authors.forename: Kamal A
authors.initials: KA
authors.lastname: Mohammed
authors.forename: Najmunnisa
authors.initials: N
authors.lastname: Nasreen
authors.forename: Veena B
authors.initials: VB
authors.lastname: Antony
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D004195:Disease Models, Animal; D016724:Empyema, Pleural / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D010994:Pleura / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D012334:RNA, Neoplasm / Q000235:genetics*; D013203:Staphylococcal Infections / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013211:Staphylococcus aureus / Q000302:isolation & purification; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494812:Bcl2l1 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012334:RNA, Neoplasm; D018808:Transcription Factor AP-1; D051020:bcl-X Protein; C052617:Bcl2 protein, mouse; D011505:Protein-Tyrosine Kinases