Bladder urothelial BK channel activity is a critical mediator for innate immune response in urinary tract infection pathogenesis.

Bladder urothelial BK channel activity is a critical mediator for innate immune response in urinary tract infection pathogenesis. Am J Physiol Renal Physiol. 2019 Jan 16;: Authors: Yeh J, Lu M, Alvarez-Lugo L, Chai TC Abstract The open probability of calcium activated voltage gated potassium channel (BK channel) on bladder umbrella urothelial cells is increased by lipopolysaccharide (LPS). It is hypothesized that this channel's activity is important in the urothelial innate immune response during urinary tract infection (UTI). We performed in vivo studies using female C57BL/6 mice whose bladders were inoculated with lipopolysaccharide (150 μl of 1 mg/mL LPS) or uropathogenic E. coli (UPEC, UTI89), without and with intravesical BK inhibitor iberiotoxin (IBTX, 1 μM). Inflammatory biomarkers (chemokines and cytokines) were measured in urine specimens collected 2 hours after inoculation using a 32-multiplex ELISA. Of these 32 biomarkers, 19 and 15, were significantly elevated two hours after LPS and UPEC exposure, respectively. IBTX significantly abrogated the elevations of 15 out of 19 biomarkers after LPS inoculation and 12 out of 15 biomarkers after UPEC inoculation. In a separate experiment, qPCR for IL-6, IP-10 (CXCL10), and MIP-2 (CXCL2) in urothelium paralleled the changes measured in urine of these same biomarkers supporting that urinary changes in biomarker levels reflected urothelial expression changes. These in vivo data dem...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research