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


     

Am J Physiol Gastrointest Liver Physiol 283: G122-G132, 2002. First published March 20, 2002; doi:10.1152/ajpgi.00015.2002
0193-1857/02 $5.00
This Article
Right arrow Full Text
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
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
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 ISI Web of Science (23)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Németh, Z. H.
Right arrow Articles by Haskó, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Németh, Z. H.
Right arrow Articles by Haskó, G.
Vol. 283, Issue 1, G122-G132, July 2002

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

Zoltán H. Németh1, Edwin A. Deitch1, Csaba Szabó1,2, Jon G. Mabley2, Pál Pacher2, Zoltán Fekete1, Carl J. Hauser1, and György Haskó1

1 Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103; and 2 Inotek Corporation, Beverly, Massachusetts 01915

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 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 interleukin-8 (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 nuclear factor-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.

cytokines; lipopolysaccharide; mitogen-activated protein kinase; Crohn's disease; ulcerative colitis


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 TABLE OF CONTENTS
Visit Other APS Journals Online