Evaluation on Potential Contributions of Protease Activated Receptors Related Mediators in Allergic Inflammation

Table 3

(a) Influence of agonists of protease activated receptors (PARs) on mediator and cytokine release from cells. (b) Influence of antagonists of protease activated receptors (PARs) on mediator and cytokine release from cells.

(a)

Agonist	Targeted cell	Response of cell
PAR-1
Thrombin	PBMC [47]; A549 [92, 93]; Mon [94]; TC [95]; HPDF [96, 97]; CHAEC [98, 99]; EnC [54]	IL-1𝛽 [47], IL-6 [47, 94, 95], IL-8 [92, 96], MCP-1 [93], MMP-9 [97], MMP-12 [99], VCAM-1 [54], VEGF [98]
Trypsin	A549 [92, 93]; Mon [94]; TC [95]	Release of IL-8 [92]; MCP-1 [93]; IL-6 [94, 95]
SFLLR-NH2	A549 [58, 92, 93]; Mon [94]; HBEC [58]; TC [95]; CHAEC [98, 99]	IL-8 [92]; MCP-1 [93]; IL-6 [94, 95]; PGE2 [58]; VEGF [98]; MMP-12 [99]
PAR-2
Tryptase	A549 [92, 93]; Neu [38]; Mon [94]; TC [95]; Astr [111]	Release of IL-8 [38, 92]; MCP-1 [93]; IL-6 [94, 95, 111]; LF [38];TNF-𝛼, ROS [111]
Trypsin	A549 [92, 93]; Mon [94]; HPBF [68]; Eos [35]; MC [107]; HUVEC [108]	Release of IL-8 [68, 92, 108]; MCP-1 [93]; IL-6 [94]; G-CSF, VCAM-1 [68]; sys-LT, ROS [35]; tryptase [107]
Elastase	A549 [92, 93]; AEC [101]; Mon [94]	Release of IL-8 [92]; MCP-1 [93]; IL-6 [94]; MUC5AC [101]
GCE	MH-S [49]; RAW264.7 [49]	TNF-𝛼 [49]
WCE	PHKC [104]	Release of IL-8, GM-CSF [104]
SLIGKV-NH2	A549 [58, 92, 93]; HPBF [68]; HBEC [58]; TC [95]; HTEC [102]; Kerat [103]; Neu [38]; Eos [35, 36]; MC [107]; BEAS-2B, Calu-3 [109]	Release of IL-8 [38, 68, 92, 109]; MCP-1 [93]; PGE2 [58]; IL-6 [95, 109]; G-CSF [68]; VCAM-1 [68, 102]; GM-CSF [102, 109]; TNF-𝛼 [102]; MMP-1,10 [102]; TSLP [103]; LF [38]; sys-LT, ROS [35]; SOD [36]; His [107]
tc-LIGRLO-NH2	Neu [38]; MC [107]	Release of IL-8, LF [38]; His [107]
PAR-3
Thrombin	A549 [92, 93]; Mon [94]; EnC [54]	Release of IL-8 [92]; MCP-1 [93]; IL-6 [94]; ICAM-1, VCAM-1 [54]
PAR-4
Thrombin	A549 [92, 93]; Mon [94]	Release of IL-8 [92]; MCP-1 [93]; IL-6 [94]
GYPGQV-NH2	A549 [58, 92, 93]; Mon [94]; HBEC [58]	IL-8 [92]; MCP-1 [93]; IL-6 [94]; PGE2 [58]

(b)

Antagonist	Targeted cell	Response of cell
PAR-1
SCH 79797	HUVEC [165]; HDF [166]; MC [29]	Block thrombin induced CX3CL1 [165]; inhibit plasmin-induced IL-8, PGE [166]; inhibit trypsin and tryptase induced IL-4 release [29]
BMS 200261	PL [114]	Inhibit PAR-1 activation in response to thrombin [114];
RWJ-56110 [122, 167]; RWJ-58259 [123]	HSC [167]; HVC, PL [112, 113]	Reduced liver type I collagen [167], reduced liver calcium mobilization, and cellular functions (platelet aggregation and cell proliferation [112, 113])
PAR-2
FSLLRY-NH2	HUVEC [108]; Astr [111]; MC [20, 29, 31, 32]	Inhibit trypsin-induced IL-8 [108]; alleviate IL-6 and TNF-𝛼 secretion [111]; inhibit trypsin and tryptase induced IL-4 release [20, 29, 31]; inhibit tryptase induced IL-13 release [32]
ENMD-1068	Eos [168]	Abolish tryptase-induced eosinophil recruitment [168]
GB88	HTEC [102]; HT29, A549, Panc-1, MKN1, MKN45, MDA-MB231, HUVEC [117]; Mac, MC [169]	Block PAR-2 agonist-induced increases in GM-CSF, IL-6, IL-8, and TNF-α [102]; ameliorate macrophage invasion and MC degranulation [169]; inhibit PAR-2 activated Ca(2+) release induced by trypsin or synthetic peptide and nonpeptide agonists [117]
PAR-4
Pepducin P4pal-10	Neu [115]	Diminish neutrophil migration mediated by neutrophil expressed PAR-4 [115]

PBMC: peripheral blood mononuclear cells; A549: A549 epithelial cells; Mon: monocyte; TC: T cell; HPDF: human primary dermal fibroblast; CHAEC: cultured human airway epithelial cell; EnC: endothelial cell; HBEC: human bronchial epithelial cell; Neu: neutrophil; Astr: astrocytes; HPBF: human primary bronchial fibroblasts; Eos: eosinophil; MC: mast cell; HUVEC: human umbilical vein endothelial cell; AEC: airway epithelial cells; MH-S: alveolar macrophage cell lines; RAW264.7: peritoneal macrophage cell lines; PHKC: primary human keratinocyte; HTEC: kidney tubular epithelial cells; Kerat: keratinocyte; BEAS-2B: human airway epithelial cell line BEAS-2B; Calu-3: human airway epithelial cell line Calu-3; HDF: human dental pulp fibroblast-like cells; PL: platelet; HSC: hepatic stellate cell; HVC: human vascular cell; HT29: human colon adenocarcinoma cell line; Panc-1: pancreas epithelioid carcinoma line Panc-1; MKN1: human gastric carcinoma cell line MKN1; MKN45: human gastric carcinoma cell line MKN45; MDA-MB231: breast adenocarcinoma cell line MDA-MB231; Mac: macrophage; IL: interleukin; MCP-1: monocyte chemoattractant protein-1; MMP: matrix metalloproteinase; VCAM: vascular cell adhesion molecule; VEGF: vascular endothelial growth factor; PG: prostaglandin; LF: lactoferrin; TNF: tumor necrosis factor; ROS: reactive oxygen species; G-CSF: granulocyte colony-stimulating factor; cys-LT: cysteinyl leukotrienes; MUC5AC: mucin5AC; GM-CSF: granulocyte-macrophage colony-stimulating factor; TSLP: thymic stromal lymphopoietin; SOD: superoxide; His: histamine; ICAM: intercellular adhesion molecule.