A novel peptide able to reduce PLA2 activity and modulate inflammatory cytokine production

Abstract

Phospholipases A₂ (PLA₂s) are associated with inflammatory response, performing a complex process involving, specially, cytokines. The excess of pro-inflammatory cytokines induces a chronic inflammatory response and can cause several disorders in the body. Therefore, the inhibition or regulation of cytokines' signaling pathways is a target for new treatment development strategies. Thus, this study aimed to select PLA₂ inhibitor mimetic peptides through phage display technology with anti-inflammatory activity. Specific mimetic peptides were selected using BpPLA2-TXI, a PLA₂ isolated from Bothrops pauloensis, as a target, and γCdcPL, a PLA₂ inhibitor isolated from Crotalus durissus collilineatus, which was used as a competitor during the elution step. We selected the peptide C2PD, which seems to play a pivotal role in the modulation of IL-6, IL-1β, and IL-10 cytokines in inflammatory cells. The C2PD showed a significant reduction in PLA₂ activity. Furthermore, the synthetic peptide was tested in PBMC and showed a significant down-modulation of IL-6 and IL-1β release, whereas IL-10 responses were up-regulated. Our findings suggest that this novel peptide may be a potential therapeutic candidate for the treatment of inflammatory diseases, mainly due to its anti-inflammatory properties and absence of cytotoxicity.

Keywords: Bothropsspp.; Crotalus durissus; Inflammatory cytokines; Phage display; Phospholipase A(2); Snake serum.