The NACHT, LRR and PYD Domains-Containing protein 3 (NLRP3) Inflammasome Mediates Inflammation and Voiding Dysfunction in a Lipopolysaccharide-Induced Rat Model of Cystitis
|Francis M Hughes Jr1,2*, James G Kennis2, Melissa N Youssef2, Danielle W Lowe3, Brooke E Shaner4 and J Todd Purves1,2,3,5|
|1Department of Surgery, Division of Urology, Duke University Medical Center, Durham, NC, USA|
|2Department of Urology, Medical University of South Carolina, Charleston, SC, USA|
|3Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA|
|4Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA|
|5Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA|
|*Corresponding Author :||Francis M Hughes Jr
Department of Surgery, Division of Urology
Duke University Medical Center, PO. Box-3831
Durham, NC 27710, USA
E-mail: [email protected]
|Received: January 24, 2016 Accepted: February 25, 2016 Published: February 29, 2016|
|Citation: Hughes Jr FM, Kennis JGBS, Youssef MN, Lowe DW, Shaner BE, et al., (2016) The NACHT, LRR and PYD Domains-Containing Protein 3 (NLRP3) Inflammasome Mediates Inflammation and Voiding Dysfunction in a Lipopolysaccharide-Induced Rat Model of Cystitis. J Clin Cell Immunol 7:396. doi:10.4172/2155-9899.1000396|
|Copyright: © 2016 Hughes Jr FM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
Objective: NOD-like receptors (NLRs) sense sterile and non-sterile signals and form inflammasomes which trigger an inflammatory response through the activation of caspase-1 and release of IL-1β. Recently we have shown the presence of several NLRs in the bladder urothelia and demonstrated the importance of NLRP3 in bladder outlet obstruction and cyclophosphamide-induced cystitis, both models of sterile inflammation. In this study we explore a role for NLRP3 in mediating the response to LPS, a key antigen of uropathogenic bacteria.
Method: In order to bypass the protective glycosaminoglycan layer lining the urothelium, LPS was directly injected into the bladder wall of Sprague-Dawley rats. Glyburide (a NLRP3 inhibitor) or vehicle was administered orally prior to and after injection. Rats were analyzed 24 h later. Inflammasome activity (caspase-1 activity, IL-1β release) and inflammation (Evan’s Blue extravasation, bladder weight) were assessed, as was physiological bladder function (urodynamics).
Results: Injection of LPS stimulated inflammasome activation (caspase-1 activity) and the release of IL-1β into the urine which was prevented by glyburide. Likewise, LPS increased inflammation, (bladder weight and the extravasation of Evan’s blue dye), and this was reversed by glyburide. Functionally, animals injected with saline alone demonstrated decreased voiding volume as measured by urodynamics. In the presence of LPS, additional urinary dysfunction was evident with decreased voiding pressures and threshold pressures. The decrease in voiding pressure was blocked by glyburide but the decrease in threshold pressure was not, suggesting that LPS has significant effects mediated by inflammasome-dependent and -independent mechanisms.
Conclusion: Overall, the results demonstrate the potential importance of inflammasomes in bacterial cystitis as well as the ability of the bladder wall injection technique to isolate the in vivo effects of specific inflammasome ligands to the physiological changes associated with cystitis.