A novel peptide able to reduce PLA 2 activity and modulate inflammatory cytokine production

• Published in: Toxicon (Oxford) Vol. 231; p. 107207
• Main Authors: Torres Costa, Kellen Cristina, Santana Vieira Santos, Vanessa, Rezende Vaz, Emília, Natalie Cirilo Gimenes, Sarah, Ian Veloso Correa, Lucas, Brito de Souza, Jessica, de Almeida Araújo Santos, Fabiana, de Melo Rodrigues, Veridiana, Ricardo Goulart, Luiz, Alonso Goulart, Vivian
• Format: Journal Article
• Language: English
• Published: England 25.06.2023
• Subjects: Crotalus durissus; Phage display; Inflammatory cytokines; Bothropsspp; Phospholipase A; Snake serum
• ISSN: 1879-3150

Phospholipases A (PLA s) 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 PLA inhibitor mimetic peptides through phage display technology with anti-inflammatory activity. Specific mimetic peptides were selected using BpPLA2-TXI, a PLA isolated from Bothrops pauloensis, as a target, and γCdcPL, a PLA 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 PLA 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.