Annexin A1 Mimetic Peptide and Piperlongumine: Anti-Inflammatory Profiles in Endotoxin-Induced Uveitis

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 11; p. 3170
• Main Authors: Girol, Ana Paula, de Freitas Zanon, Caroline, Caruso, Ícaro Putinhon, de Souza Costa, Sara, Souza, Helena Ribeiro, Cornélio, Marinônio Lopes, Oliani, Sonia Maria
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15-11-2021; MDPI
• Subjects: Ac2-26; Animals; Annexin A1 - administration & dosage; Annexin A1 - pharmacology; Annexin A1 - therapeutic use; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Binding sites; Blindness; Cell growth; Cilia - enzymology; Cilia - pathology; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Dioxolanes - administration & dosage; Dioxolanes - pharmacology; Dioxolanes - therapeutic use; Endotoxins; Eye - drug effects; Eye - pathology; eye inflammation; FPR receptor; Gene expression; Inflammation; Inflammation Mediators - metabolism; inflammatory mediators; Inoculation; Investigations; Leukocytes (mononuclear); lipopolysaccharide; Lipopolysaccharides; Lung cancer; Male; Models, Biological; Monocytes - drug effects; natural bioactive extracts; Neutrophils - drug effects; Peptides; Peptides - administration & dosage; Peptides - pharmacology; Peptides - therapeutic use; Phosphorylation; Proteins; Rats; Rats, Wistar; Receptors, Lipoxin - metabolism; Tumor necrosis factor-TNF; Uveitis; Uveitis - blood; Uveitis - chemically induced; Uveitis - drug therapy; Uveitis - pathology; inflammatory mediators; FPR receptor; eye inflammation; Ac2-26; lipopolysaccharide; natural bioactive extracts
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10113170

Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis.