Activation of human monocytes by a formyl peptide receptor 2-derived pepducin

Abstract 

We synthesized and investigated the effect of formyl peptide receptor 2 (FPR2)-derived pepducins in human monocytes. The FPR2-based cell-penetrating lipopeptide, “pepducin” (F2pal-16), stimulated intracellular calcium increase in human monocytes via pertussis toxin (PTX)-sensitive G-protein and phospholipase C (PLC) activity. From a functional aspect, we showed that F2pal-16 stimulated monocyte chemotaxis. F2pal-16 also stimulated the generation of superoxide anion in human monocytes. Moreover, F2pal-16 dramatically increased the production of several kinds of pro-inflammatory cytokines (CXCL8, CCL2, IL-1β and TNF-α) in human monocytes via NF-κB activation. Since FPR2 plays an important role in immune responses, F2pal-16 can serve as a useful reagent for the study of FPR2-mediated immune modulation.

Abbreviations: FPR2, formyl peptide receptor 2, SAA, serum amyloid A, GPCR, G-protein coupled receptor, PTX, pertussis toxin, MAPKs, mitogen activated protein kinases, [Ca²⁺]_i, intracellular calcium concentration, HPF, high-power fields, WRW⁴, WRWWWW, PLC, phospholipase C

Keywords: FPR2, Pepducin, Monocytes, Chemotaxis, Pertussis toxin-sensitive G-protein, Cytokine