Authors

Akosua Vilaysane, Justin Chun, Mark E. Seamone, Wenjie Wang, Rick Chin, Simon Hirota, Yan Li, Sharon A. Clark, Jurg Tschopp, Kiril Trpkov, Brenda R. Hemmelgarn, Paul L. Beck, and Daniel A. Muruve

Details

First Published in the Journal of the American Society of Nephrology (JASN) August 5, 2010,
J Am Soc Nephrol. 2010 Oct;21(10):1732-44. Epub 2010 Aug 5.
Read the article online at JASN view the PDF version or read online at PMC NIH

Abstract

Inflammation significantly contributes to the progression of chronic kidney disease (CKD). Inflammasome-dependent cytokines, such as IL-1β and IL-18, play a role in CKD, but their regulation during renal injury is unknown. Here, we analyzed the processing of caspase-1, IL-1β, and IL-18 after unilateral ureteral obstruction (UUO) in mice, which suggested activation of the Nlrp3 inflammasome during renal injury. Compared with wild-type mice, Nlrp3(-/-) ...

Authors

Jeffrey Ng 1, Simon A Hirota, Olaf Gross, Yan Li, Annegret Ulke-Lemee, Mireille S Potentier, L Patrick Schenck, Akosua Vilaysane, Mark E Seamone, Hanping Feng, Glen D Armstrong, Jurg Tschopp, Justin A Macdonald, Daniel A Muruve, Paul L Beck

Overview

First published in the American Gastroenterology Association (AGA) journal, Gastroenterology, April 13 2010
Gastroenterology. 2010 Aug;139(2):542-52, 552.e1-3. Epub 2010 Apr 13.
PMID: 20398664 DOI: 10.1053/j.gastro.2010.04.005
Read the full article online at Gastroenterology view the PDF version or read online at PMC NIH

BACKGROUND & AIMS: Clostridium difficile-associated disease (CDAD) is the leading cause of nosocomial diarrhea in the United States. C difficile toxins TcdA and TcdB breach the intestinal barrier and trigger mucosal inflammation and intestinal damage. The inflammasome is an intracellular danger sensor of the innate immune system. In the present study, we hypothesize that TcdA and TcdB trigger inflammasome-dependent interleukin (IL)-1beta ...

Authors

LiMei Wang, Jennifer J Rahn, XueQing Lun, Beichen Sun, John J. P Kelly, Samuel Weiss, Stephen M Robbins, Peter A Forsyth, and Donna L Senger

Details

Published in PLoS Biology. 2008 Nov; 6(11): e289.,
Published online 2008 Nov 25. doi: 10.1371/journal.pbio.0060289
Read the full article at PLoS Biology or at NIH PMC

Abstract

The multifunctional signaling protein p75 neurotrophin receptor (p75(NTR)) is a central regulator and major contributor to the highly invasive nature of malignant gliomas. Here, we show that neurotrophin-dependent regulated intramembrane proteolysis (RIP) of p75(NTR) is required for p75(NTR)-mediated glioma invasion, and identify a previously unnamed process for targeted glioma therapy. Expression of cleavage-resistant chimeras of p75(NTR) or treatment of animals bearing p75(NTR)-positive intracranial tumors with clinically applicable gamma-secretase inhibitors resulted in dramatically decreased glioma invasion and prolonged survival. Importantly, proteolytic processing of p75(NTR) was observed in ...