Document Detail

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR(2) ) is involved in vascular function.
MedLine Citation:
PMID:  22957757     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR(2) and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models.
EXPERIMENTAL APPROACH: Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR(2) activating peptide (AP) was used as a PAR(2) agonist. Aortas harvested from TLR4(-/-) mice were also used to characterize the PAR(2) response.
KEY RESULTS: PAR(2) , but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR(2) AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR(2) AP-induced vasorelaxation and PAR(2) AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4(-/-) mice, the expression of PAR(2) was reduced and the PAR(2) AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective.
CONCLUSIONS AND IMPLICATIONS: Cross-talk between PAR(2) and TLR4 contributes to vascular homeostasis.
M Bucci; V Vellecco; L Harrington; V Brancaleone; F Roviezzo; G Mattace Raso; A Ianaro; G Lungarella; R De Palma; R Meli; G Cirino
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  168     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-06-17     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  411-20     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
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MeSH Terms
Aorta, Thoracic / physiology*
Hypotension / chemically induced,  physiopathology
Mice, Inbred C57BL
Mice, Knockout
Rats, Wistar
Receptor, PAR-2 / physiology*
Toll-Like Receptor 4 / physiology*
Vasodilation / physiology
Reg. No./Substance:
0/2-furoyl-LIGRLO-amide; 0/Lipopolysaccharides; 0/Oligopeptides; 0/Receptor, PAR-2; 0/Tlr4 protein, mouse; 0/Tlr4 protein, rat; 0/Toll-Like Receptor 4

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