Gonococcal porin IB activates NF-kappaB in human urethral epithelium and increases the expression of host antiapoptotic factors.
Infection of human urethral epithelial cells (UECs) with Neisseria gonorrhoeae increases the transcription of several host antiapoptotic genes, including bfl-1, cox-2, and c-IAP-2. In order to identify the bacterial factor(s) responsible for eliciting these changes, the transcriptional status of apoptotic machinery was monitored in UECs challenged with certain gonococcal membrane components. Initially, we observed that infection of UECs with gentamicin-killed gonococci increased the expression of the antiapoptotic Bcl-2 family member, bfl-1. This observation indicated that viable, replicating bacteria are not required for induction of antiapoptotic gene expression. Confirming this observation, treatment of UECs with purified gonococcal membrane increased the expression of bfl-1, cox-2, and c-IAP-2. This finding suggested that a factor or multiple factors present in the outer membrane (OM) are responsible for altering UEC antiapoptotic gene expression. Interestingly, treatment of UECs with gonococcal porin IB (PorB IB), a major constituent of the OM, significantly increased the transcription of bfl-1, cox-2, and c-IAP-2. The upregulation of these genes by PorB IB was determined to be dependent on NF-kappaB activation, as inhibiting NF-kappaB blocked induced expression of these genes. This work demonstrates the altered expression of host apoptotic factors in response to gonococcal PorB IB and supports a model whereby UEC cell death may be modulated as a potential mechanism of bacterial survival and proliferation.
Binnicker
Matthew J
MJ
Department of Microbiology, University of Iowa, Iowa City 52242, USA.
Williams
Richard D
RD
Apicella
Michael A
MA
D017209:Apoptosis / Q000187:drug effects*; D002461:Cell Line, Transformed; D051546:Cyclooxygenase 2; D004847:Epithelial Cells / Q000382:microbiology; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity*; D018272:Porins / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014521:Urethra / Q000166:cytology / Q000382:microbiology*
C096816:BCL2-related protein A1; D007527:Isoenzymes; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; D018272:Porins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C057699:porin protein, Neisseria; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases