ANXA1Ac2–26 peptide, a possible therapeutic approach in inflammatory ocular diseases

Abstract

The eye is immunologically privileged when inflammatory responses are suppressed. One component responsible for the suppression of inflammatory responses is the blood retinal barrier, which comprises the retinal pigment epithelium. The destruction of this barrier initiates inflammation, which can affect any part of the eye. Therefore, inflammatory response is controlled by the action of anti-inflammatory mediators, among these mediators, annexin A1 (ANXA1) protein acts as a modulator of inflammation. In this study we aimed to improve the knowledge of this area by investigating how a peptide of the ANXA1 protein (ANXA1) modulates the morphology, proliferation, migration and expression of genes and proteins in human retinal pigment epithelium cells (ARPE-19). Determining how signaling pathways (NF-κB and UBC) are modulated by the ANXA1 peptide could be important for understanding the inflammatory process. ARPE-19 cells were activated by bacterial lipopolysaccharide endotoxin (LPS) and treated with ANXA1 peptide, in a concentration of 1.7μM and 33.8μM. We observed that the LPS activation diminished the levels of endogenous ANXA1 after 2h and 24h and ANXA1 peptide decreased the proliferation and re-establishes the migration of ARPE-19 cells. After using a hybridization approach, 80 differentially expressed genes were found. Five of these genes were selected (LRAT, CTGF, MAP1B, ALDH1A3 and SETD7) and all were down-regulated after treatment with the peptide. The genes CTGF and LRAT would be considered as potential molecular markers of ophthalmologic inflammation. The expression of pro-inflammatory cytokines was also decreased after the treatment, indicating the efficiency of the anti-inflammatory peptide at high concentrations, since the reduction in the levels of these mediators were observed after the treatment with ANXA1 peptide at 33.8μM. Our results suggest that the retinal pigment epithelial cells are a potential target of the ANXA1 protein and point to possible applications of the ANXA1 peptide as an innovative therapy for the treatment of ocular inflammation.

Annexin A12–26 Treatment Improves Skin Heterologous Transplantation by Modulating Inflammation and Angiogenesis Processes

“…It is commonly known that acellular skin is not able to promote a specific inflammatory reaction in response to a local graft ( Sengor et al, 2005 ; Ngo et al, 2011 ), but inflammation occurs due to invasive surgical procedures, and the exacerbated inflammatory reaction impairs tissue regeneration ( Diegelmann and Evans, 2004 ). Since the initial phase, the AnxA1 2–26 was able to reduce the expression of IL-1β, INF-γ, IL-6, TNF-α, and IL-17, corroborating studies with in vivo and in vitro models of retina autoimmune disease and uveitis in rodents and human ( Girol et al, 2013 ; Yazid et al, 2015 ; Cardin et al, 2017 ). Lima et al (2017) showed that AnxA1 can acts at multiple regulatory levels to promote resolution of inflammation and may be a common mechanism that account for the pro-resolving actions of pro-resolving molecules.…”

Genome-Wide Association Analysis Identified ANXA1 Associated with Shoulder Impingement Syndrome in UK Biobank Samples

“…One vital finding of this study is the two significant risk SNPs rs754832 and rs750968, both of them were near to the ANXA1 (Annexin A1) gene on chromosome nine. This gene encodes a membrane-localized protein that inhibits phospholipase A2 and has anti-inflammatory activity ( Cardin et al 2017 ). A research identified the regulation of the inflammation by regulating the clearance of neutrophils by macrophages in mouse bone marrow as a critical regulator role for the anti-inflammatory molecule ANXA1 (Dali et al 2012).…”

Silencing of Annexin A1 suppressed the apoptosis and inflammatory response of preeclampsia rat trophoblasts

“…ANXA1 was demonstrated to exhibit various anti-inflammatory properties ( 40 ). Researchers have reported that ANXA1 Ac2-26 peptide reduced the inflammatory response in ARPE-19 cells and peritonitis rats ( 41 , 42 ). However, ANXA1 is also modulated by pro-inflammatory proteins, suggesting that it may act as a ‘brake’ in controlling the inflammatory response ( 43 ).…”