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

Author(s)

Girol, Ana Paula ^{[1, 2, 3]} ; Zanon, Caroline de Freitas ^[2] ; Caruso, Icaro Putinhon ^[4] ; Costa, Sara de Souza ^{[1, 2]} ; Souza, Helena Ribeiro ^{[1, 2]} ; Cornelio, Marinonio Lopes ^[4] ; Oliani, Sonia Maria ^{[2, 3, 5]}

Affiliation

^[1] Univ Ctr Padre Albino UNIFIPA, Dept Phys & Morphol Sci, BR-15809144 Catanduva, SP - Brazil

^[2] Sao Paulo State Univ, Inst Biosci Humanities & Exact Sci Ibilce, Dept Biol, UNESP, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[3] Univ Fed Sao Paulo, Escola Paulista Med UNIFESP EPM, Post Grad Program Struct & Funct Biol, BR-04023062 Sao Paulo, SP - Brazil

^[4] Sao Paulo State Univ, Inst Biosci, Dept Phis, UNESP, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[5] Uniao Fac Grandes Lagos Unilago, Adv Res Ctr Med CEPAM, BR-15030070 Sao Jose Do Rio Preto, SP - Brazil

• Document type: Journal article
• Source: CELLS; v. 10, n. 11 NOV 2021.
• Web of Science Citations: 0

Abstract

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 mu g), PL (200 and 400 mu g), 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. (AU)

• FAPESP's process: 15/03359-5 - Endotoxin-induced uveitis: analysis of the interaction Annexin A1 and natural bioactive extracts as an alternative therapy
• Grantee: Ana Paula Girol
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/19949-7 - Evaluation of annexin A1 protein immunomodulatory activity in cutaneous and placental lesions resulting from Diabetes Mellitus
• Grantee: Sonia Maria Oliani
• Support Opportunities: Regular Research Grants