Exposure to C. Albicans Makes Bladder Epithelial Cells Induce Apoptosis and Modification of Their Microenvironment

Abstract INTRODUCTION. Interstitial cystitis/painful bladder syndrome (IC) is characterized by chronic bladder pain and urinary storage symptoms. IC affects more than 3.3 million women in the U.S. alone. Ibis T-5000 assays and next generation sequencing have revealed that the C. albicans fungus is highly abundant in the urine of IC patients, particularly those who report greater pain, urinary urgency, and flares. However, currently, the clinical significance of C. albicans in the urine remains elusive. Here, we report the pathological effects and mechanisms triggered by C. albicans in a healthy normal bladder. METHODS. Immortalized bladder epithelial cells were infected with C. albicans. Perturbations in gene expression were identified using an Affymetrix gene microarray and subsequently followed with bioinformatic analyses, including gene set enrichment. Inflammatory and apoptotic genes were quantified using RT-PCR and Western blot analyses. Central signal pathways were examined using Western blot analysis. RESULTS. DNA microarray analysis showed alterations in the transcriptome of bladder epithelial cells infected with C. albicans over both the short and long terms. Key inflammatory and apoptosis networks were changed, which was consistent with several cellular events. Cellular levels of reactive oxygen species and nitrogen oxide increased after infection. Productions of cyclooxygenase-2 and prostaglandine E2 also increased after C. albicans infection, and their productions were suppressed by blockage of reactive oxygen species-epidermal growth factor receptor-Erk pathway. CONCLUSIONS. This study provides evidence that C. albicans infection triggers inflammation and cellular damage by dysregulating key regulatory genes, signaling pathways, and bioactive species in normal bladder cells.