Document Detail


Glucose activation of islets of Langerhans up-regulates Toll-like receptor 5: possible mechanism of protection.
MedLine Citation:
PMID:  21985371     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Toll-like receptors are pattern-recognition receptors of the innate immune system that are activated during viral, bacterial or other infections, as well as during disease progression of type 1 and type 2 diabetes. Toll-like receptor 5 (TLR-5) specifically recognizes bacterial infection through binding of flagellin from pathogenic bacteria such as Salmonella and Listeria species. We have found that the expression of TLR5 is up-regulated by glucose activation of isolated islets of Langerhans, in contrast to other investigated TLRs (TLR-2, -3, -4, -6 and -9. Stimulation of islets with 10 mm glucose increased the levels of TLR5 mRNA 10-fold (P=0·03) and the TLR-5 protein levels twofold (P=0·04). Furthermore, the protein level of downstream signalling molecule myeloid differentiation primary response gene 88 (MyD88) increased 1·6-fold (P=0·01). Activation of TLR-5 in islets lead to a marked reduction of both stimulated and basal secretion of insulin, as well as an increase in production of nitric oxide, proinflammatory cytokines, anti-inflammatory heat-shock protein and major histocompatibility complex (MHC) class I transporter. We observe no effects of TLR-5 activation on islet survival. We suggest that this regulation by TLR-5 might be beneficial during serious infection such as sepsis by limiting the activity of beta cells during peaks of insulin demand to counteract beta cell damage.
Authors:
C Weile; K Josefsen; K Buschard
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  166     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-11     Completed Date:  2011-11-28     Revised Date:  2011-11-30    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  251-7     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.
Affiliation:
The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark. cweile@yahoo.dk
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Tumor
Cytokines / biosynthesis
Glucose / metabolism*
Heat-Shock Proteins / biosynthesis
Inflammation / immunology,  metabolism
Insulin / secretion
Islets of Langerhans / metabolism*
Major Histocompatibility Complex / drug effects
Male
Mice
Mice, Inbred BALB C
Myeloid Differentiation Factor 88 / biosynthesis,  metabolism
Nitric Oxide / biosynthesis
RNA, Messenger / genetics,  metabolism
Rats
Rats, Inbred Lew
Reverse Transcriptase Polymerase Chain Reaction
Toll-Like Receptor 5 / genetics,  immunology,  metabolism*
Chemical
Reg. No./Substance:
0/Cytokines; 0/Heat-Shock Proteins; 0/Insulin; 0/Myd88 protein, mouse; 0/Myeloid Differentiation Factor 88; 0/RNA, Messenger; 0/Toll-Like Receptor 5; 10102-43-9/Nitric Oxide; 50-99-7/Glucose

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


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