AJP - GI Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol (March 20, 2002). doi:10.1152/ajpgi.00015.2002
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
283/1/G122    most recent
00015.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nemeth, Z. H
Right arrow Articles by Hasko, G.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Nemeth, Z. H
Right arrow Articles by Hasko, G.

Articles in PresS, published online ahead of print March 20, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00015.2002
Submitted on January 14, 2002
Accepted on March 15, 2002

Na+/H+ exchanger blockade inhibits the enterocyte inflammatory response and protects against colitis

Zoltan H Nemeth1, Edwin A Deitch1, Csaba Szabo2, Jon G Mabley3, Pal Pacher3, Zoltan Fekete1, Carl J Hauser1, and Gyorgy Hasko1*

1 Department of Surgery, UMD-New Jersey Medical School, Newark, NJ, USA
2 Inotek Corp., Beverly, MA, USA; Department of Surgery, UMD-New Jersey Medical School, Newark, NJ, USA
3 Inotek Corp., Beverly, MA, USA

* To whom correspondence should be addressed. E-mail: haskoge{at}umdnj.edu.

Na+/H+ exchangers (NHEs) are integral transmembrane proteins found in all mammalian cells. There is substantial evidence indicating that NHEs regulate inflammatory processes. Because intestinal epithelial cells express a variety of NHEs, we tested the possibility that NHEs are also involved in the regulation of the epithelial cell inflammatory response. In addition, since the epithelial inflammatory response is an important contributor to mucosal inflammation in inflammatory bowel disease (IBD), we examined the role of NHEs in the modulation of disease activity in a mouse model of IBD. In human gut epithelial cells, NHE inhibition using a variety of agents, including amiloride, 5-(N-methyl-N-isobutyl)amiloride, 5-(N-ethyl-N-isopropyl)-amiloride, harmaline, clonidine, and cimetidine suppressed IL-8 production. The inhibitory effect of NHE inhibition on IL-8 was associated with a decrease in IL-8 mRNA accumulation. NHE inhibition suppressed both activation of the p42/p44 mitogen-activated protein kinase and NF-{kappa}B. Finally, NHE inhibition ameliorated the course of IBD in dextran sulfate-treated mice. Our data demonstrate that inhibition of NHEs may be an approach worthy of pursuing for the treatment of IBD.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
G. Hecht, K. Hodges, R. K. Gill, F. Kear, S. Tyagi, J. Malakooti, K. Ramaswamy, and P. K. Dudeja
Differential regulation of Na+/H+ exchange isoform activities by enteropathogenic E. coli in human intestinal epithelial cells
Am J Physiol Gastrointest Liver Physiol, August 1, 2004; 287(2): G370 - G378.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. V. Mukhin, M. N. Garnovskaya, M. E. Ullian, and J. R. Raymond
ERK Is Regulated by Sodium-Proton Exchanger in Rat Aortic Vascular Smooth Muscle Cells
J. Biol. Chem., January 16, 2004; 279(3): 1845 - 1852.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. G. Mabley, P. Pacher, L. Liaudet, F. G. Soriano, G. Hasko, A. Marton, C. Szabo, and A. L. Salzman
Inosine reduces inflammation and improves survival in a murine model of colitis
Am J Physiol Gastrointest Liver Physiol, January 1, 2003; 284(1): G138 - G144.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1979 by the American Physiological Society.