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

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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.
Costa KCT, Santos VSV, Vaz ER, Gimenes SNC. A novel peptide able to reduce PLA2 activity and modulate inflammatory cytokine production. Toxicon. 2023 Aug; 231:107207. doi:10.1016/j.toxicon.2023.107207.
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