Format

Send to

Choose Destination
Am J Physiol Gastrointest Liver Physiol. 2013 Jan 1;304(1):G12-25. doi: 10.1152/ajpgi.00201.2012. Epub 2012 Nov 1.

Critical role of interleukin-17A in murine intestinal ischemia-reperfusion injury.

Author information

1
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032-3784, USA. tl128@columbia.edu

Abstract

Intestinal ischemia-reperfusion (I/R) injury causes severe illness frequently complicated by remote multiorgan dysfunction and sepsis. Recent studies implicated interleukin-17A (IL-17A) in regulating inflammation, autoimmunity, and I/R injury. Here, we determined whether IL-17A is critical for generation of intestinal I/R injury and subsequent liver and kidney injury. Mice subjected to 30 min of superior mesenteric artery ischemia not only developed severe small intestinal injury (necrosis, apoptosis, and neutrophil infiltration) but also developed significant renal and hepatic injury. We detected large increases in IL-17A in the small intestine, liver, and plasma. IL-17A is critical for generating these injuries, since genetic deletion of IL-17A- or IL-17A-neutralizing antibody treatment markedly protected against intestinal I/R injury and subsequent liver and kidney dysfunction. Intestinal I/R caused greater increases in portal plasma and small intestine IL-17A, suggesting an intestinal source for IL-17A generation. We also observed that intestinal I/R caused rapid small intestinal Paneth cell degranulation and induced murine α-defensin cryptdin-1 expression. Furthermore, genetic or pharmacological depletion of Paneth cells significantly attenuated the intestinal I/R injury as well as hepatic and renal dysfunction. Finally, Paneth cell depletion significantly decreased small intestinal, hepatic, and plasma IL-17A levels after intestinal I/R. Taken together, we propose that Paneth cell-derived IL-17A may play a critical role in intestinal I/R injury as well as extraintestinal organ dysfunction.

PMID:
23125155
DOI:
10.1152/ajpgi.00201.2012
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center