Document Detail


Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.
MedLine Citation:
PMID:  23028934     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the hosts production of the antimicrobial agent nitric oxide (NO). A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consumes arginine as main energy source and secretes an arginine-consuming enzyme, arginine deiminase (ADI). Reduced intestinal epithelial cell (IEC) proliferation is a common theme during bacterial and viral intestinal infections, but it has never been connected to arginine-consumption. Our specific question was thereby, whether the arginine-consumption by Giardia leads to reduced IEC proliferation, in addition to NO reduction. In vitro cultivation of human IEC lines in arginine-free or arginine/citrulline-complemented medium, as well as in interaction with different G. intestinalis isolates, were used to study effects on host cell replication by MTT assay. IEC proliferation was further analyzed by DNA content analysis, polyamine measurements and expressional analysis of cell cycle regulatory genes. IEC proliferation was reduced upon arginine-withdrawal and also in an arginine-dependent manner upon interaction with G. intestinalis or addition of Giardia ADI. We show that arginine-withdrawal by intestinal pathogens leads to a halt in the cell cycle in IECs through reduced polyamine levels and upregulated cell cycle inhibitory genes. This is of importance with regards to intestinal tissue homeostasis that is affected through reduced cell proliferation. Thus, the slower epithelial cell turnover helps the pathogen to maintain a more stable niche for colonization. This study also shows why supplementation therapy of diarrhea patients with arginine/citrulline is helpful and that citrulline especially should gain further attention in future treatment strategies.
Authors:
Britta Stadelmann; María C Merino; Lo Persson; Staffan G Svärd
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-19
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-02-25     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e45325     Citation Subset:  IM    
Affiliation:
Department of Cell and Molecular Biology, Biomedical Centre Uppsala, University of Uppsala, Uppsala, Sweden. britta.stadelmann@icm.uu.se
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MeSH Terms
Descriptor/Qualifier:
Arginine / metabolism*
Caco-2 Cells
Cell Cycle / physiology
Cell Proliferation
Epithelial Cells / parasitology*
Giardia lamblia / metabolism*,  pathogenicity*
Humans
Hydrolases / metabolism
Intestines / cytology*
Ornithine Carbamoyltransferase / metabolism
Polyamines / metabolism
Chemical
Reg. No./Substance:
0/Polyamines; 74-79-3/Arginine; EC 2.1.3.3/Ornithine Carbamoyltransferase; EC 3.-/Hydrolases; EC 3.5.3.6/arginine deiminase
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