Infection of human urethral epithelium with Neisseria gonorrhoeae elicits an upregulation of host anti-apoptotic factors and protects cells from staurosporine-induced apoptosis.
In order to better understand the host response to an infection with Neisseria gonorrhoeae, microarray technology was used to analyse the gene expression profile between uninfected and infected human urethral epithelium. The anti-apoptotic genes bfl-1, cox-2 and c-IAP-2 were identified to be upregulated approximately eight-, four- or twofold, respectively, following infection. Subsequent assays including RT-PCR, real time RT-PCR and RNase protection confirmed the increased expression of these apoptotic regulators, and identified that a fourth anti-apoptotic factor, mcl-1, is also upregulated. RT-PCR and RNase protection also showed that key pro-apoptotic factors including bax, bad and bak do not change in expression. Furthermore, our studies demonstrated that infection with the gonococcus partially protects urethral epithelium from apoptosis induced by the protein kinase inhibitor, staurosporine (STS). This work shows that following infection with Neisseria gonorrhoeae, several host anti-apoptotic factors are upregulated. In addition, a gonococcal infection protects host cells from subsequent STS-induced death. The regulation of host cell death by the gonococcus may represent a mechanism employed by this pathogen to survive and proliferate in host epithelium.
Binnicker
Matthew J
MJ
Department of Microbiology, The University of Iowa, Iowa City 52242, USA.
Williams
Richard D
RD
Apicella
Michael A
MA
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D020869:Gene Expression Profiling; D019254:Genes, bcl-2 / Q000187:drug effects; D006069:Gonorrhea / Q000235:genetics / Q000473:pathology; D006801:Humans; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity*; D020411:Oligonucleotide Array Sequence Analysis; D047428:Protein Kinase Inhibitors; D019311:Staurosporine / Q000494:pharmacology; D015854:Up-Regulation; D014521:Urethra / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology*
D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D019311:Staurosporine