Table 7.

Intracellular signaling cascades triggered by endogenous nonpeptide ligands.

Ligand	Origin	Selectivity	Cells	Effects	Ref.	Potency
LXA4	Eicosanoids	FPR2	Epith. and Endothel. cells; Neutrophils	NO production; inhibition of neutrophil infiltration and transmigration	[93–95]	pKd = 8.77 EC50 = 50 nM
			Neutrophils	chemotaxis; Ca2+ mobilization; PKC-dependent PLD activation	[96]
			Renal mesangial cells	inhibition of LTD4- and LXA4-induced cell proliferation and PI3K activity; ERKs and p38MAPK phosphorylation; inhibition of PDGF-Rβ and EGF-R; p21cip1 and p27kip1 modulation; inhibition of PDGF-induced increase of CDK2/cyclin E complex; block of G1-S progression	[97,98]
			HLF	inhibition of CTGF-induced cell proliferation, of ERKs, PI3K and Akt phosphorylation, of cyclin D1 expression and of STAT3 DNA-binding activity; p27kip1 modulation	[99]
			MCF-7; MDA-MB-231	increase in cyclin D1; Akt and p79S6K phosphorylation	[81]
			Synovial fibroblasts	inhibition of IL-1β-induced IL-6, IL-8 and MMP-3 synthesis of FPR2 expression; downregulation of IL-1β-induced AP1 and NF-κB DNA binding activity	[100,101]
			Dendritic cells	induction of SOCS-2	[106]
Rv	Lipid mediator	GPCR-32, FPR2	Salivary cells	cell migration; polarity; inhibition of TNF-α-induced cytoskeletal disruption; modulation of PI3K/Akt pathway	[108]	-
D1		FPR2	Acute lung injury	decrement of IL-1β, IL-6, TNF-α and of NF-κB p65 translocation	[109]
		FPR2	Inflamed adipose tissue	secretion of adiponectin; decreased pro-inflammatory adipokine production	[110]

LXA4, lipoxin A4; GPCR, G-protein coupled receptor; HLF, human lung fibroblast; PDGF, platelet-derived growth factor; CTGF, connective tissue growth factor; Epith. and Endothel. cells, Epithelial and Endothelial cells; pKd, negative logarithm of Kd.