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

Ana Paula Girol,Marinônio Lopes Cornélio,Helena Ribeiro Souza,Sara De Souza Costa,Caroline De Freitas Zanon,Sonia Maria Oliani,Ícaro Putinhon Caruso

doi:10.3390/cells10113170

Ana Paula Girol, Marinônio Lopes Cornélio + Show 5 more

Open Access

https://doi.org/10.3390/cells10113170

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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 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.

Highlights

Uveitis is an intraocular inflammation of different etiologies [1,2,3,4,5] characterized by leukocyte accumulation in ocular tissues and cytokine release
Transmigrated leukocytes were absent in the control eyes (Figure 2A), but a high influx of these cells, mainly neutrophils, occurred 24 h after LPS inoculation without treatment (Figure 2B)
The anterior eye segment was the most affected, and the inflammatory cells were observed in aqueous humor (AqH), anterior and posterior chambers, and in iris, ciliary body, and ciliary process stroma (Figure 2B)

Summary

Introduction

Uveitis is an intraocular inflammation of different etiologies [1,2,3,4,5] characterized by leukocyte accumulation in ocular tissues and cytokine release. It is a painful condition and is associated with redness, photophobia, impaired vision, and blindness [6,7,8,9,10]. Recent advances in the mechanisms of inflammation and the discovery of several endogenous anti-inflammatory mediators have provided new therapeutic possibilities for uveitis treatment [5,7,10,13,14,15].

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