Document Detail

Metal allergens nickel and cobalt facilitate TLR4 homodimerization independently of MD2.
MedLine Citation:
PMID:  23059983     Owner:  NLM     Status:  MEDLINE    
Development of contact allergy requires cooperation of adaptive and innate immunity. Ni(2+) stimulates innate immunity via TLR4/MD2, the bacterial LPS receptor. This likely involves receptor dimerization, but direct proof is pending and it is unclear if related haptens share this mechanism. We reveal Co(2+) as second metal stimulating TLR4 and confirm necessity of H456/H458 therein. Experiments with a new TLR4 dimerization mutant established dimerization as a mechanism of metal- and LPS-induced TLR4 activation. Yet, in interaction studies only LPS- but not metal-induced dimerization required MD2. Consistently, soluble TLR4 expressed without MD2 inhibited metal- but not LPS-induced responses, opening new therapeutic perspectives.
Badrinarayanan Raghavan; Stefan F Martin; Philipp R Esser; Matthias Goebeler; Marc Schmidt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-12
Journal Detail:
Title:  EMBO reports     Volume:  13     ISSN:  1469-3178     ISO Abbreviation:  EMBO Rep.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-30     Completed Date:  2013-05-30     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  100963049     Medline TA:  EMBO Rep     Country:  England    
Other Details:
Languages:  eng     Pagination:  1109-15     Citation Subset:  IM    
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MeSH Terms
Adaptive Immunity / genetics
Allergens / toxicity
Cobalt / toxicity*
Dermatitis, Allergic Contact* / genetics,  immunology,  metabolism
Human Umbilical Vein Endothelial Cells / drug effects
Immunity, Innate / genetics
Inflammation / chemically induced,  metabolism
Lipopolysaccharides / immunology,  metabolism
Lymphocyte Antigen 96* / chemistry,  genetics,  metabolism
Mutant Proteins / chemistry,  genetics,  metabolism
Nickel / toxicity*
Protein Multimerization
Signal Transduction / immunology
T-Lymphocytes / drug effects,  immunology
Toll-Like Receptor 4* / chemistry,  genetics,  metabolism
Reg. No./Substance:
0/Allergens; 0/LY96 protein, human; 0/Lipopolysaccharides; 0/Lymphocyte Antigen 96; 0/Mutant Proteins; 0/TLR4 protein, human; 0/Toll-Like Receptor 4; 3G0H8C9362/Cobalt; 7OV03QG267/Nickel

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

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