title: Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR(2) ) is involved in vascular function.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  Cross-talk between PAR(2)  and TLR4 contributes to vascular homeostasis.
authors.affiliation: Department of Experimental Pharmacology, Faculty of Pharmacy, University of Naples 'Federico II', Napoli, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bucci
authors.forename: V
authors.initials: V
authors.lastname: Vellecco
authors.forename: L
authors.initials: L
authors.lastname: Harrington
authors.forename: V
authors.initials: V
authors.lastname: Brancaleone
authors.forename: F
authors.initials: F
authors.lastname: Roviezzo
authors.forename: G
authors.initials: G
authors.lastname: Mattace Raso
authors.forename: A
authors.initials: A
authors.lastname: Ianaro
authors.forename: G
authors.initials: G
authors.lastname: Lungarella
authors.forename: R
authors.initials: R
authors.lastname: De Palma
authors.forename: R
authors.initials: R
authors.lastname: Meli
authors.forename: G
authors.initials: G
authors.lastname: Cirino
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009842:Oligopeptides; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology
chemical_list: C487404:2-furoyl-LIGRLO-amide; D008070:Lipopolysaccharides; D009842:Oligopeptides; D044464:Receptor, PAR-2; C493487:Tlr4 protein, mouse; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4