A novel peptide able to reduce PLA2 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 Correia, 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: Elsevier Ltd 01.08.2023
• Subjects: Bothropsspp; Crotalus durissus; Inflammatory cytokines; Phage display; Phospholipase A2; Snake serum; Crotalus durissus; Bothropsspp; Phage display; Phospholipase A2; Inflammatory cytokines; Snake serum
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2023.107207

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. [Display omitted] •The performed Phage Display has created C2PD peptide.•C2PD peptide had no harmful effect on PBMC.•Both C2PD and PLA2 inhibitor interact with important PLA2 amino acid residues.•C2PD peptide was able to reduce the PLA2 activity.•C2PD promoted modulation of IL-6, IL-1β and IL-10 cytokines.