The potential repertoire of the innate immune system in the bladder: expression of pattern recognition receptors in the rat bladder and a rat urothelial cell line (MYP3 cells).

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2015-12

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Abstract

The urothelium is a frontline sensor of the lower urinary tract, sampling the bladder lumen and stimulating an immune response to infectious and noxious agents. Pattern recognition receptors (PRRs) recognize such agents and coordinate the innate response, often by forming inflammasomes that activate caspase-1 and the release of interleukin-1. We have shown the presence of one PRR (NLRP3) in the urothelia and its central role in the inflammatory response to cyclophosphamide. The purpose of this study was to (1) assess the likely range of the PPR response by assessing the repertoire present in the rat bladder and (2) determine the utility of the MYP3 rat urothelia cell line for in vitro studies by assessing its PPR repertoire and functional responsiveness.Immunohistochemistry was performed for seven PPRs (NLRP1, NLRP3, NLRP6, NLRP7, NLRP12, NLRC4 and AIM2) on bladder sections and MYP3 cells. For functionality, MYP3 cells were challenged with the quintessential NLRP3 activator ATP and assessed for caspase-1 activation.All PPRs examined were expressed in the bladder and localized to the urothelial layer with several also in the detrusor (none in the interstitia). MYP3 cells also expressed all PRRs with a variable intracellular location. ATP-stimulated caspase-1 activity in MYP3 cells in a dose-dependent manner was reduced by knockdown of NLRP3 expression.The results suggest that the bladder possesses the capacity to initiate an innate immune response to a wide array of uropathological agents and the MYP3 cells will provide an excellent investigational tool for this field.

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10.1007/s11255-015-1126-6

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Hughes, Francis M, David P Turner and J Todd Purves (2015). The potential repertoire of the innate immune system in the bladder: expression of pattern recognition receptors in the rat bladder and a rat urothelial cell line (MYP3 cells). International urology and nephrology, 47(12). pp. 1953–1964. 10.1007/s11255-015-1126-6 Retrieved from https://hdl.handle.net/10161/17177.

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Hughes

Monty Hughes

Assistant Professor in Urology

 Dr. Hughes received his Ph.D. from the Medical University of South Carolina and was a post doc at both the University of North Carolina at Chapel Hill and NIH. He then joined the faculty of the University of North Carolina at Charlotte where he rose to the rank of Associate Professor (with tenure). Following a brief stint as the director of the biology division of a start-up pharmaceutical company, he joined forces with Dr. Purves at the Medical University of South Carolina to begin this lab focused on benign urinary disorders. Dr. Hughes has been at Duke since 2015. He is currently an Assistant Professor working within the Department of Surgery and Division of Urology. He serves as the Director of the Urinary Dysfunction Laboratory which studies the role of inflammation in disorders such as bladder outlet obstruction and diabetic bladder dysfunction. In association with Dr. J Todd Purves, this lab has been instrumental in demonstrating the central importance of the NLRP3 inflammasome in sensing the biochemical stressors associated with these disorders and translating them into an inflammatory signal. This signal is ultimately responsible for changes in voiding function, denervation and fibrosis.


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