Document Detail

Soluble MD2 increases TLR4 levels on the epithelial cell surface.
MedLine Citation:
PMID:  18845299     Owner:  NLM     Status:  MEDLINE    
The accessory protein MD2 has been implicated in LPS-mediated activation of the innate immune system by functioning as a co-receptor with TLR4 for LPS binding at the cell surface. Epithelial cells that play a role in primary immune response, such as in the lung or gut, often express TLR4, but are dependent on circulating soluble MD2 (sMD2) to bind TLR4 to assemble the functional receptor. In this study, we show that sMD2 incubation with HEK293 epithelial cells transfected with TLR4 increases the cell surface levels of TLR4 in the absence of LPS. Dose response studies reveal that a threshold sMD2 concentration (approximately 450 nM) stimulates maximal TLR4 levels on the cell surface, whereas higher concentrations of sMD2 (approximately 1800 nM) reduce these enhanced TLR4 levels. We show evidence that MD2 multimer formation is increased at these higher concentrations of sMD2 and that addition of LPS to sMD2-stimulated cells masks the enhanced TLR4 cell surface levels, most likely due to the LPS-induced downregulation of TLR4 by endocytosis following receptor stimulation. All together, these results support a model in which sMD2 binds to TLR4 and increases TLR4 levels at the cell surface by preventing TLR4 turnover through the endocytic pathway. Thus, sMD2 may prime epithelial cells for enhanced immunoresponsive function prior to LPS exposure.
Sabine Lauer; Yuliya A Kunde; Theresa A Apodaca; Byron Goldstein; Elizabeth Hong-Geller
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-10-09
Journal Detail:
Title:  Cellular immunology     Volume:  255     ISSN:  1090-2163     ISO Abbreviation:  Cell. Immunol.     Publication Date:  2009  
Date Detail:
Created Date:  2009-02-10     Completed Date:  2009-03-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1246405     Medline TA:  Cell Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8-16     Citation Subset:  IM    
Bioscience Division, Los Alamos National Laboratory, P.O. Box 1663, MS-M888, Los Alamos, NM 87545, USA.
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MeSH Terms
Cell Line
Cell Membrane / metabolism*
Epithelial Cells / cytology,  metabolism*
Lipopolysaccharides / immunology
Lymphocyte Antigen 96 / genetics,  immunology*
Toll-Like Receptor 4 / genetics,  immunology*
Reg. No./Substance:
0/LY96 protein, human; 0/Lipopolysaccharides; 0/Lymphocyte Antigen 96; 0/Toll-Like Receptor 4

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