E-Posters-10180

10180_Yeh
Pdf Summary
Researchers at Yale School of Medicine have discovered that the large conductance voltage-gated calcium-activated potassium (BK) channel plays a critical role in regulating the release of cytokines in the bladder urothelium during urinary tract infections (UTIs). The bladder urothelium acts as the first line of defense against uropathogens and initiates the innate immune response. The researchers previously identified the presence of the BK channel in bladder urothelial cells and observed an increase in its activity when exposed to lipopolysaccharide (LPS), a surrogate for gram-negative bacteria. In this study, they aimed to determine if the increase in BK channel activity regulates cytokine release.<br /><br />Using a murine model, the researchers treated female mice with LPS and measured the urinary concentrations of 32 cytokines. They found that LPS significantly increased the levels of 19 cytokines. However, when they pretreated the mice with iberiotoxin (IBTX), a BK channel blocker, the urinary concentrations of 15 of these cytokines were significantly reduced. Additionally, the researchers analyzed urothelial RNA expression for select cytokines and found that the LPS-induced upregulation of cytokine expression was significantly inhibited by IBTX.<br /><br />These findings provide the first in vivo evidence that the BK channel in the bladder urothelium regulates the innate immune response to uropathogens. The researchers suggest that targeting the BK channel could be a potential strategy for developing future treatments for urinary tract infections. This study was supported by the Women's Health Research at Yale (WHRY) Naratil Pioneer Award.<br /><br />In summary, the study demonstrates that the BK channel plays a crucial role in regulating cytokine release in the bladder urothelium during urinary tract infections. By blocking the BK channel with IBTX, the researchers observed a significant reduction in cytokine levels. This discovery provides new insights into the urothelial innate immune response and may contribute to the development of novel therapies for UTIs.
Keywords
Yale School of Medicine
BK channel
cytokine release
bladder urothelium
urinary tract infections
innate immune response
lipopolysaccharide
urothelial RNA expression
BK channel blocker
novel therapies