Autor(es): Cardin, Laila Toniol [UNESP] ; Sonehara, Nathália Martins [UNESP] ; Mimura, Kallyne Kioko Oliveira [UNESP] ; Ramos Dinarte dos Santos, Anemari ; da Silva, Wilson Araújo ; Sobral, Lays Martin ; Leopoldino, Andréia Machado ; da Cunha, Bianca Rodrigues ; Tajara, Eloiza H. ; Oliani, Sonia Maria [UNESP] ; Rodrigues-Lisoni, Flávia Cristina [UNESP]
Data: 2018
Identificador Persistente: http://hdl.handle.net/11449/174522
Origem: Oasisbr
Made available in DSpace on 2018-12-11T17:11:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-05-30
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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 (ANXA1Ac2–26) 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 ANXA1Ac2–26 peptide could be important for understanding the inflammatory process. ARPE-19 cells were activated by bacterial lipopolysaccharide endotoxin (LPS) and treated with ANXA1Ac2–26 peptide, in a concentration of 1.7 μM and 33.8 μM. We observed that the LPS activation diminished the levels of endogenous ANXA1 after 2 h and 24 h and ANXA1Ac2–26 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 ANXA1Ac2–26 peptide at 33.8 μM. Our results suggest that the retinal pigment epithelial cells are a potential target of the ANXA1 protein and point to possible applications of the ANXA1Ac2–26 peptide as an innovative therapy for the treatment of ocular inflammation.
Department of Biology Institute of Biosciences Letters and Science — IBILCE/UNESP
Department of Clinical Medical Foundation Blood Center of Ribeirão Preto Faculty of Medicine of Ribeirão Preto University of São Paulo — FCFRP/USP
Department of Clinical Analyses Toxicology and Food Science Faculty of Pharmaceutical Science of Ribeirão Preto University of São Paulo – FCFRP/USP
Department of Molecular Biology Faculty of Medicine of São José do Rio Preto — FAMERP
Department of Biology and Animal Science Faculty of Engineering of Ilha Solteira — FEIS/UNESP
Department of Biology Institute of Biosciences Letters and Science — IBILCE/UNESP
Department of Biology and Animal Science Faculty of Engineering of Ilha Solteira — FEIS/UNESP
FAPESP: 2012/08320-1
FAPESP: 2013/24083-2
FAPESP: 2016/02012-4
CNPq: 308144/2014-7
