Document Detail


Hydrocortisone modulates cholera toxin endocytosis by regulating immature enterocyte plasma membrane phospholipids.
MedLine Citation:
PMID:  18456000     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Diarrheal disease is a major cause of morbidity and mortality in infants and children worldwide. Evidence has indicated immature human enterocytes and their interaction with bacteria and enterotoxins may account for the noted increased susceptibility of neonates to diarrhea. Our aim was to characterize the developmental difference in cholera toxin (CT)-GM1-mediated endocytosis.
METHODS: We used H4 cells (a fetal human small intestinal epithelial cell line), T84 cells, primary cultured mature human small intestinal epithelial cells, and human fetal small intestine xenografts. In addition, hydrocortisone was used as a potent intestinal trophic factor to induce maturation of the human enterocytes.
RESULTS: Here we show an increase in CT-caveolae and a decrease in CT-clathrin colocalization in H4/hydrocortisone compared with H4 cells by electron microscopy. In T84 and freshly isolated human small intestinal epithelial cells, a significant amount of GM1 was partitioned into the lipid rafts. In contrast, there was little CT-GM1/lipid raft association in H4 cells. However, hydrocortisone significantly increased GM1/lipid raft association in H4 cells. Furthermore, we noted an increase in the level of phosphatidylcholine, sphingomyelin, and the ratio of phosphatidylcholine/phosphatidylinositol in mature compared with immature enterocytes and that hydrocortisone can accelerate this maturational process. Disruption of phosphatidylinositol transfer protein alpha using small interference RNA showed an increase in GM1/lipid raft association in H4 cells and resulted in a decreased CT response.
CONCLUSIONS: Our studies suggest that the developmental change in CT endocytosis is partially caused by an increased GM1-lipid raft association through a maturational change of phospholipid composition on the cell surface of immature enterocytes.
Authors:
Lei Lu; Yuanwu Bao; Abdullah Khan; Allan M Goldstein; David S Newburg; Andrea Quaroni; Dennis Brown; W Allan Walker
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-03-22
Journal Detail:
Title:  Gastroenterology     Volume:  135     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-08     Completed Date:  2008-08-08     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  185-193.e1     Citation Subset:  AIM; IM    
Affiliation:
Developmental Gastroenterology Laboratory, Massachusetts General Hospital for Children, Boston, Massachusetts, USA. lul@helix.mgh.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Adjuvants, Immunologic / pharmacokinetics*
Animals
Anti-Inflammatory Agents / pharmacology*
Cell Differentiation
Cell Membrane / metabolism,  ultrastructure
Cells, Cultured
Cholera Toxin / pharmacokinetics*
Endocytosis / drug effects*,  physiology
Enterocytes / drug effects,  metabolism*,  ultrastructure
Humans
Hydrocortisone / pharmacology*
Immunohistochemistry
Intestinal Mucosa / cytology,  drug effects,  metabolism*
Intestine, Small / cytology
Mice
Mice, SCID
Microscopy, Immunoelectron
Phospholipids / metabolism
Transplantation, Heterologous
Grant Support
ID/Acronym/Agency:
P-30-DK 40561/DK/NIDDK NIH HHS; P01 DK033506-230015/DK/NIDDK NIH HHS; P01-DK33506/DK/NIDDK NIH HHS; P30 DK040561-13/DK/NIDDK NIH HHS; R01 HD031852-10/HD/NICHD NIH HHS; R01-DK70260/DK/NIDDK NIH HHS; R37 HD012437-27/HD/NICHD NIH HHS; R37-HD12437/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Anti-Inflammatory Agents; 0/Phospholipids; 50-23-7/Hydrocortisone; 9012-63-9/Cholera Toxin
Comments/Corrections

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