RGD Reference Report - Anti-inflammatory mechanisms of the annexin A1 protein and its mimetic peptide Ac2-26 in models of ocular inflammation in vivo and in vitro. - Rat Genome Database

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Anti-inflammatory mechanisms of the annexin A1 protein and its mimetic peptide Ac2-26 in models of ocular inflammation in vivo and in vitro.

Authors: Girol, AP  Mimura, KK  Drewes, CC  Bolonheis, SM  Solito, E  Farsky, SH  Gil, CD  Oliani, SM 
Citation: Girol AP, etal., J Immunol. 2013 Jun 1;190(11):5689-701. doi: 10.4049/jimmunol.1202030. Epub 2013 May 3.
RGD ID: 7421538
Pubmed: PMID:23645879   (View Abstract at PubMed)
DOI: DOI:10.4049/jimmunol.1202030   (Journal Full-text)

Annexin A1 (AnxA1) is a protein that displays potent anti-inflammatory properties, but its expression in eye tissue and its role in ocular inflammatory diseases have not been well studied. We investigated the mechanism of action and potential uses of AnxA1 and its mimetic peptide (Ac2-26) in the endotoxin-induced uveitis (EIU) rodent model and in human ARPE-19 cells activated by LPS. In rats, analysis of untreated EIU after 24 and 48 h or EIU treated with topical applications or with a single s.c. injection of Ac2-26 revealed the anti-inflammatory actions of Ac2-26 on leukocyte infiltration and on the release of inflammatory mediators; the systemic administration of Boc2, a formylated peptide receptor (fpr) antagonist, abrogated the peptide's protective effects. Moreover, AnxA1(-/-) mice exhibited exacerbated EIU compared with wild-type animals. Immunohistochemical studies of ocular tissue showed a specific AnxA1 posttranslational modification in EIU and indicated that the fpr2 receptor mediated the anti-inflammatory actions of AnxA1. In vitro studies confirmed the roles of AnxA1 and fpr2 and the protective effects of Ac2-26 on the release of chemical mediators in ARPE-19 cells. Molecular analysis of NF-kappaB translocation and IL-6, IL-8, and cyclooxygenase-2 gene expression indicated that the protective effects of AnxA1 occur independently of the NF-kappaB signaling pathway and possibly in a posttranscriptional manner. Together, our data highlight the role of AnxA1 in ocular inflammation, especially uveitis, and suggest the use of AnxA1 or its mimetic peptide Ac2-26 as a therapeutic approach.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
uveitis treatmentISOAnxa1 (Rattus norvegicus)7421538; 7421538 RGD 
uveitis  ISOAnxa1 (Mus musculus)7421538; 7421538 RGD 
uveitis treatmentIDA 7421538 RGD 
uveitis  IMP 7421538 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Anxa1  (annexin A1)

Genes (Mus musculus)
Anxa1  (annexin A1)

Genes (Homo sapiens)
ANXA1  (annexin A1)


Additional Information