Neurokinin-1 (NK-1) receptor is required in Clostridium difficile- induced enteritis

Ignazio Castagliuolo, Martin Riegler, Asiya Pasha, Sigfus Nikulasson, Bao Lu, Craig Gerard, Norma P. Gerard, Charalabos Pothoulakis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

155 Citations (Scopus)

Abstract

Toxin A, a 308,000-M(r) enterotoxin from Clostridium difficile, mediates antibiotic-associated diarrhea and colitis in humans. Injection of toxin A into animal intestine triggers an acute inflammatory response characterized by activation of sensory neurons and immune cells of the intestinal lamina propria, including mast cells and macrophages, and migration of circulating neutrophils in the involved intestinal segment. In this study we show that mice genetically deficient in the neurokinin-1 receptor are protected from the secretory and inflammatory changes as well as from epithelial cell damage induced by toxin A. The protective effect of neurokinin-1R deletion correlates with diminished intestinal levels of the cytokine TNF-α and its mRNA and the leukocyte enzyme myeloperoxidase. These results demonstrate a major requirement for substance Preceptors in the pathogenesis of acute inflammatory diarrhea.

Original languageEnglish
Pages (from-to)1547-1550
Number of pages4
JournalJournal of Clinical Investigation
Volume101
Issue number8
DOIs
Publication statusPublished - 15 Apr 1998

Other keywords

  • Clostridium difficile
  • Enterotoxins
  • Intestinal inflammation
  • Neurokinin-1 receptor
  • Substance P

Fingerprint

Dive into the research topics of 'Neurokinin-1 (NK-1) receptor is required in Clostridium difficile- induced enteritis'. Together they form a unique fingerprint.

Cite this