Document Detail


Reduced inflammatory potential of peritoneal macrophages recruited in mice pretreated with a glycolipid synthesis inhibitor.
MedLine Citation:
PMID:  16983496     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Integral components of mammalian cell membranes, glycosphingolipids (GSL) reside in specialized plasma membrane microdomains critical for cell signaling. N-alkylated nojirimycins are compounds developed for GSL substrate deprivation therapy, blocking GSL synthesis by specifically inhibiting an essential enzyme, ceramide glucosyltransferase. Peritoneal macrophages recruited in mice pretreated with an inhibitory N-alkylnojirimycin displayed a reduced capacity to release either TNFalpha or interleukin-6 when re-exposed to whole killed E. coli in vitro. Cell viability and protein content were not affected. A nojirimycin analogue without GSL inhibitory capacity had no effect. The results show inhibition of GSL synthesis in vivo by an N-alkylnojirimycin can reduce the response to an inflammatory stimulus and indicate N-alkylnojirimycins have experimental and potential clinical value for modulating innate immune responses in vivo.
Authors:
H C Yohe; T J Kitzmiller; W J Bement; B E Dwyer; J F Sinclair
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Inflammopharmacology     Volume:  14     ISSN:  0925-4692     ISO Abbreviation:  Inflammopharmacology     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-09-19     Completed Date:  2006-10-13     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9112626     Medline TA:  Inflammopharmacology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  170-5     Citation Subset:  IM    
Affiliation:
Research Service, Department of Veterans Affairs, VA RO & MC, 215 North Main Street, White River Junction, VT 05009, USA. herbert.c.yohe@dartmouth.edu
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MeSH Terms
Descriptor/Qualifier:
1-Deoxynojirimycin / analogs & derivatives
Animals
Cell Survival / drug effects
Cytokines / metabolism
Enzyme Inhibitors / pharmacology*
Glucosamine / analogs & derivatives*,  pharmacology
Glucosyltransferases / antagonists & inhibitors*
Glycosphingolipids / antagonists & inhibitors*,  biosynthesis
Immunity, Innate / drug effects*
Macrophages, Peritoneal* / drug effects,  enzymology,  immunology,  metabolism
Mice
Mice, Inbred C3H
Chemical
Reg. No./Substance:
0/Cytokines; 0/Enzyme Inhibitors; 0/Glycosphingolipids; 15218-38-9/nojirimycin; 19130-96-2/1-Deoxynojirimycin; 3416-24-8/Glucosamine; EC 2.4.1.-/Glucosyltransferases; EC 2.4.1.80/ceramide glucosyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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