Nitric oxide synthase stimulates prostaglandin synthesis and barrier function inC. parvum-infected porcine ileum
Open Access
- 1 September 2004
- journal article
- Published by American Physiological Society in American Journal of Physiology-Gastrointestinal and Liver Physiology
- Vol. 287 (3), G571-G581
- https://doi.org/10.1152/ajpgi.00413.2003
Abstract
Cell culture models implicate increased nitric oxide (NO) synthesis as a cause of mucosal hyperpermeability in intestinal epithelial infection. NO may also mediate a multitude of subepithelial events, including activation of cyclooxygenases. We examined whether NO promotes barrier function via prostaglandin synthesis using Cryptosporidium parvum-infected ileal epithelium in residence with an intact submucosa. Expression of NO synthase (NOS) isoforms was examined by real-time RT-PCR of ileal mucosa from control and C. parvum-infected piglets. The isoforms mediating and mechanism of NO action on barrier function were assessed by measuring transepithelial resistance (TER) and eicosanoid synthesis by ileal mucosa mounted in Ussing chambers in the presence of selective and nonselective NOS inhibitors and after rescue with exogenous prostaglandins. C. parvum infection results in induction of mucosal inducible NOS (iNOS), increased synthesis of NO and PGE2, and increased mucosal permeability. Nonselective inhibition of NOS ( NG-nitro-l-arginine methyl ester) inhibited prostaglandin synthesis, resulting in further increases in paracellular permeability. Baseline permeability was restored in the absence of NO by exogenous PGE2. Selective inhibition of iNOS [l- N6-(1-iminoethyl)-l-lysine] accounted for ∼50% of NOS-dependent PGE2synthesis and TER. Using an entire intestinal mucosa, we have demonstrated for the first time that NO serves as a proximal mediator of PGE2synthesis and barrier function in C. parvum infection. Expression of iNOS by infected mucosa was without detriment to overall barrier function and may serve to promote clearance of infected enterocytes.Keywords
This publication has 38 references indexed in Scilit:
- Oral Bovine Serum Concentrate Improves Cryptosporidial Enteritis in CalvesPediatric Research, 2002
- Lactulose–Mannitol Intestinal Permeability Test in Children With Diarrhea Caused by Rotavirus and CryptosporidiumJournal of Pediatric Gastroenterology and Nutrition, 2000
- Reactive Oxygen Metabolites in Piglet CryptosporidiosisPediatric Research, 1997
- Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammationGastroenterology, 1997
- Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitisGastroenterology, 1995
- Intestinal function and injury in acquired immunodeficiency syndrome—related cryptosporidiosisGastroenterology, 1995
- Tumour necrosis factor alpha changes porcine intestinal ion transport through a paracrine mechanism involving prostaglandins.Gut, 1994
- Cryptosporidium parvum Infection of Intestinal Epithelium: Morphologic and Functional Studies in an In Vitro ModelThe Journal of Infectious Diseases, 1994
- Nitric oxide: an endogenous modulator of leukocyte adhesion.Proceedings of the National Academy of Sciences of the United States of America, 1991
- Partitioning of paracellular conductance along the ileal crypt-villus axis: A hypothesis based on structural analysis with detailed consideration of tight junction structure-function relationshipsThe Journal of Membrane Biology, 1984