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Review
. 2014:2014:829068.
doi: 10.1155/2014/829068. Epub 2014 Apr 30.

Evaluation on potential contributions of protease activated receptors related mediators in allergic inflammation

Huiyun Zhang  1 , Xiaoning Zeng  2 , Shaoheng He  3
Affiliations
Review

Evaluation on potential contributions of protease activated receptors related mediators in allergic inflammation

Huiyun Zhang et al. Mediators Inflamm. 2014.

Abstract

Protease activated receptors (PARs) have been recognized as a distinctive four-member family of seven transmembrane G protein-coupled receptors (GPCRs) that can be cleaved by certain serine proteases. In recent years, there has been considerable interest in the role of PARs in allergic inflammation, the fundamental pathologic changes of allergy, but the potential roles of PARs in allergy remain obscure. Since many of these proteases are produced and actively involved in the pathologic process of inflammation including exudation of plasma components, inflammatory cell infiltration, and tissue damage and repair, PARs appear to make important contribution to allergy. The aim of the present review is to summarize the expression of PARs in inflammatory and structural cells, the influence of agonists or antagonists of PARs on cell behavior, and the involvement of PARs in allergic disorders, which will help us to better understand the roles of serine proteases and PARs in allergy.

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Figures

Figure 1
Figure 1
Activation mechanism of protease activated receptor (PAR). PARs are a group of four G protein-coupled receptors (GPCRs). Activation of PARs depends on the protease cleavage at the specific site of the extracellular N-terminal, upon which the exposed tethered ligand (gray square) binds to the second extracellular loop of PAR resulting in a series of cellular signaling events. The red arrow indicates cleavage site. The site for PAR-1 is at LDPR41↓S42FLLRN, PAR-2 is at SKGR34↓S35SLIGKV, PAR-3 is at LPIK38↓T39FRGAP, and PAR-4 is at PAPR47↓G48 YPGQV. PAR-2 antagonist peptide: FSLLRY-NH2; SCH 79797: a PAR-1 antagonist; the active peptides were PAR-1: SFLLR-NH2, TFLLRN-NH2; PAR-2: SLIGKV-NH2, transcinnamoyl- (tc-) LIGRLO-NH2; and PAR-3: TFRGAP-NH2 PAR-4, GYPGQV-NH2. S = Ser, F = Phe, L = Leu, R = Arg, T = Thr, I = Ile, G = Gly, K = Lys, V = Val, O = Pyl, A = Ala, P = Pro, Y = Tyr, Q = Gln, and V = Val.
Figure 2
Figure 2
(a) Signal transduction pathways for PAR-1 and PAR-2. (b) Signal transduction pathways for PAR-1 and PAR-3. (c) Signal transduction pathways for PAR-4.
Figure 3
Figure 3
(a) Potential roles of agonists of PARs in allergic inflammation. (b) Potential roles of antagonists of PARs in allergic inflammation.
See this image and copyright information in PMC

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