| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
INFLAMMATION/IMMUNITY/MEDIATORS
1Division of Gastroenterology, British Columbia’s Children’s Hospital, Vancouver, British Columbia, V6H 3V4; 3Intestinal Diseases Research Program and Department of Medicine, McMaster University, Hamilton, Ontario, L8N 3Z5 Canada; 2Departments of Gastroenterology and Pathology, University Hospital, Groningen, the Netherlands; and 4Department of Veterans Affairs Medical Center, West Roxbury, Massachusetts General Hospital, Boston, Massachusetts 02132
Submitted 26 April 2004 ; accepted in final form 16 June 2004
The role of nitric oxide (NO) in inflammatory bowel diseases has traditionally focused on the inducible form of NO synthase (iNOS). However, the constitutive endothelial (eNOS) and neuronal (nNOS) isoforms may also impact on colitis, either by contributing to the inflammation or by regulating mucosal integrity in response to noxious stimuli. To date, studies examining the roles of the NOS isoforms in experimental colitis have been conflicting, and the mechanisms by which these enzymes exert their effects remain unclear. To investigate and clarify the roles of the NOS isoforms in gut inflammation, we induced trinitrobenzenesulfonic acid colitis in eNOS, nNOS, and iNOS knockout (KO) mice, assessing the course of colitis at early and late times. Both eNOS and iNOS KO mice developed a more severe colitis compared with wild-type mice. During colitis, iNOS expression dramatically increased on epithelial and lamina propria mononuclear cells, whereas eNOS expression remained localized to endothelial cells. Electron and fluorescence microscopy identified bacteria in the ulcerated colonic mucosa of eNOS KO mice, but not in wild-type, iNOS, or nNOS KO mice. Furthermore, eNOS KO mice had fewer colonic goblet cells, impaired mucin production, and exhibited increased susceptibility to an inflammatory stimulus that was subthreshold to other mice. This susceptibility was reversible, because the NO donor isosorbide dinitrate normalized goblet cell numbers and ameliorated subsequent colitis in eNOS KO mice. These results identify a protective role for both iNOS and eNOS during colitis, with eNOS deficiency resulting in impaired intestinal defense against lumenal bacteria and increased susceptibility to colitis.
mucus; bacteria; inflammatory bowel diseases; goblet cells
This article has been cited by other articles:
|
|
 |
|
  J. Petersson, O. Schreiber, A. Steege, A. Patzak, A. Hellsten, M. Phillipson, and L. Holm eNOS involved in colitis-induced mucosal blood flow increase Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1281 - G1287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sitmo, M. Rehn, and M. Diener Stimulation of voltage-dependent Ca2+ channels by NO at rat myenteric neurons Am J Physiol Gastrointest Liver Physiol, October 1, 2007; 293(4): G886 - G893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Chidlow Jr., D. Shukla, M. B. Grisham, and C. G. Kevil Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G5 - G18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ying and L. J. Hofseth An Emerging Role for Endothelial Nitric Oxide Synthase in Chronic Inflammation and Cancer Cancer Res., February 15, 2007; 67(4): 1407 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Shah, K. Morimura, and F. J. Gonzalez Expression of peroxisome proliferator-activated receptor-{gamma} in macrophage suppresses experimentally induced colitis Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G657 - G666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Rabelink and A.-J. van Zonneveld Coupling eNOS Uncoupling to the Innate Immune Response. Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2585 - 2587. [Full Text] [PDF]
|
|
|
|
|
|
T. J. Rabelink and T. F. Luscher Endothelial Nitric Oxide Synthase: Host Defense Enzyme of the Endothelium? Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 267 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rehn, D. Hild, and M. Diener Upregulation of cyclooxygenase-2 and thromboxane A2 production mediate the action of tumor necrosis factor-{alpha} in isolated rat myenteric ganglia Am J Physiol Gastrointest Liver Physiol, September 1, 2005; 289(3): G586 - G591. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
