Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR) is involved in vascular function

M. Bucci, V. Vellecco, Louise Harrington, V. Brancaleone, F. Roviezzo, G. Mattace Raso, A. Ianaro, G. Lungarella, R. De Palma, R. Meli

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)411-420
Number of pages10
JournalBritish Journal of Pharmacology
Volume168
Issue number2
DOIs
Publication statusPublished - 1 Jan 2013

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