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

Author(s):  
Jayoung Kim ◽  
Austin Yeon ◽  
Khandakar Tanvir Ahmed ◽  
Wei Zhang ◽  
Khae-Hawn Kim ◽  
...  

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.

2021 ◽  
Author(s):  
Jayoung Kim ◽  
Austin Yeon ◽  
Khandakar Ahmed ◽  
Wei Zhang ◽  
Khae-Hawn Kim ◽  
...  

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.


2018 ◽  
Vol 16 (1) ◽  
pp. 298-305
Author(s):  
Ming Wu ◽  
Min Hu ◽  
Huansheng Tong ◽  
Junying Liu ◽  
Hui Jiang ◽  
...  

AbstractKidney ischemia and hypoxia can cause renal cell apoptosis and activation of inflammatory cells, which lead to the release of inflammatory factors and ultimately result in the damage of kidney tissue and the whole body. Renal tubular cell and macrophage autophagy can reduce the production of reactive oxygen species (ROS), thereby reducing the activation of inflammatory cytoplasm and its key effector protein, caspase-1, which reduces the expression of IL-1β and IL-18 and other inflammatory factors. Ulinastatin (UTI), as a glycoprotein drug, inhibits the activity of multiple proteases and reduces myocardial damage caused by ischemia-reperfusion by upregulating autophagy. However, it can be raised by macrophage autophagy, reduce the production of ROS, and ultimately reduce the expression of inflammatory mediators, thereby reducing renal cell injury, promote renal function recovery is not clear. In this study, a series of cell experiments have shown that ulinastatin is reduced by regulating the autophagy of renal tubular epithelial cells and macrophages to reduce the production of reactive oxygen species and inflammatory factors (TNF-α, IL-1β and IL-1), and then, increase the activity of the cells under the sugar oxygen deprivation model. The simultaneous use of cellular autophagy agonists Rapamycin (RAPA) and ulinastatin has a synergistic effect on the production of reactive oxygen species and the expression of inflammatory factors.


mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Dean A. Rowe-Magnus ◽  
Adenine Y. Kao ◽  
Antonio Cembellin Prieto ◽  
Meng Pu ◽  
Cheng Kao

ABSTRACT All metazoans produce antimicrobial peptides (AMPs) that have both broad antimicrobial and immunomodulatory activity. Cathelicidins are AMPs that preferentially kill Gram-negative bacteria in vitro, purportedly by assembling into higher-order structures that perforate the membrane. We utilized high-resolution, single-cell fluorescence microscopy to examine their mechanism of action in real time. Engineered cathelicidins rapidly bound to Gram-negative and Gram-positive cells and penetrated the cytoplasmic membrane. Rapid failure of the peptidoglycan superstructure in regions of active turnover caused leakage of cytoplasmic contents and the formation of membrane-bound blebs. A mutation anticipated to destabilize interactions between cathelicidin subunits had no effect on bactericidal activity, suggesting that cathelicidins have activities beyond perforating the membrane. Nanomolar concentrations of cathelicidins, although not bactericidal, reduced the growth rate of Gram-negative and Gram-positive bacteria. The cells exhibited expression changes in multiple essential processes, including protein synthesis, peptidoglycan biosynthesis, respiration, and the detoxification of reactive oxygen species (ROS). Time-lapse imaging revealed that ROS accumulation preceded bleb formation, and treatments that reduced cellular ROS levels overcame these bactericidal effects. We propose that that the primary effect of cathelicidins is to induce the production of ROS that damage bacterial molecules, leading to slowed growth or cell death. Given their low circulating levels in vivo, AMPs may serve to slow bacterial population expansion so that cellular immunity systems can respond to and battle the infection. IMPORTANCE Antimicrobial peptides (AMPs) are an important part of the mammalian innate immune system in the battle against microbial infection. How AMPs function to control bacteria is not clear, as nearly all activity studies use nonphysiological levels of AMPs. We monitored peptide action in live bacterial cells over short time frames with single-cell resolution and found that the primary effect of cathelicidin peptides is to increase the production of oxidative molecules that cause cellular damage in Gram-positive and Gram-negative bacteria.


1995 ◽  
Vol 10 (12) ◽  
pp. 1138-1144 ◽  
Author(s):  
Xianglin Shi ◽  
Yan Mao ◽  
Lambert N. Danie ◽  
Umberto Saffiotti ◽  
Nar S. Dalal ◽  
...  

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