TY - JOUR
T1 - Neurokinin-1 (NK-1) receptor is required in Clostridium difficile- induced enteritis
AU - Castagliuolo, Ignazio
AU - Riegler, Martin
AU - Pasha, Asiya
AU - Nikulasson, Sigfus
AU - Lu, Bao
AU - Gerard, Craig
AU - Gerard, Norma P.
AU - Pothoulakis, Charalabos
PY - 1998/4/15
Y1 - 1998/4/15
N2 - 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.
AB - 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.
KW - Clostridium difficile
KW - Enterotoxins
KW - Intestinal inflammation
KW - Neurokinin-1 receptor
KW - Substance P
UR - http://www.scopus.com/inward/record.url?scp=0032523213&partnerID=8YFLogxK
U2 - 10.1172/JCI2039
DO - 10.1172/JCI2039
M3 - Article
C2 - 9541482
AN - SCOPUS:0032523213
SN - 0021-9738
VL - 101
SP - 1547
EP - 1550
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 8
ER -