title: Annexin A1 promotes timely resolution of inflammation in murine gout.
abstract: Gout is a self-limited inflammatory disease caused by deposition of monosodium urate (MSU) crystals in the joints. Resolution of inflammation is an active process leading to restoration of tissue homeostasis. Here, we studied the role of Annexin A1 (AnxA1), a glucocorticoid-regulated protein that has anti-inflammatory and proresolving actions, in resolution of acute gouty inflammation. Injection of MSU crystals in the knee joint of mice induced inflammation that was associated with expression of AnxA1 during the resolving phase of inflammation. Neutralization of AnxA1 with antiserum or blockade of its receptor with BOC-1 (nonselective) or WRW4(selective) prevented the spontaneous resolution of gout. There was greater neutrophil infiltration after challenge with MSU crystals in AnxA1 knockout mice (AnxA1-/-) and delayed resolution associated to decreased neutrophil apoptosis and efferocytosis. Pretreatment of mice with AnxA1-active N-terminal peptide (Ac2-26) decreased neutrophil influx, IL-1β, and CXCL1 production in periarticular joint. Posttreatment with Ac2-26decreased neutrophil accumulation, IL-1β, and hypernociception, and improved the articular histopathological score. Importantly, the therapeutic effects of Ac2-26were associated with increased neutrophils apoptosis and shortened resolution intervals. In conclusion, AnxA1 plays a crucial role in the context of acute gouty inflammation by promoting timely resolution of inflammation.
authors.affiliation: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Izabela
authors.initials: I
authors.lastname: Galvão
authors.affiliation: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.|Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Juliana P
authors.initials: JP
authors.lastname: Vago
authors.affiliation: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Livia C
authors.initials: LC
authors.lastname: Barroso
authors.affiliation: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Luciana P
authors.initials: LP
authors.lastname: Tavares
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Celso M
authors.initials: CM
authors.lastname: Queiroz-Junior
authors.affiliation: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Vivian V
authors.initials: VV
authors.lastname: Costa
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Carneiro
authors.affiliation: Laboratório de Inflamação, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Tatiana P
authors.initials: TP
authors.lastname: Ferreira
authors.affiliation: Laboratório de Inflamação, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Patricia M R
authors.initials: PM
authors.lastname: Silva
authors.affiliation: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Flávio A
authors.initials: FA
authors.lastname: Amaral
authors.affiliation: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.|Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Lirlândia P
authors.initials: LP
authors.lastname: Sousa
authors.affiliation: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D019138:Antibodies, Blocking / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D006073:Gout / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D007596:Joints / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000008:administration & dosage; D010455:Peptides / Q000627:therapeutic use*; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics; D014527:Uric Acid
chemical_list: D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D019138:Antibodies, Blocking; D009842:Oligopeptides; D010455:Peptides; C096153:annexin A1 peptide (2-26); C509690:tryptophyl-arginyl-tryptophyl-tryptophyl-tryptophyl-tryptophanamide; D014527:Uric Acid; C046832:t-butyloxycarbonyl-methionyl-leucyl-phenylalanine
keywords: Annexin A1; Gout; Inflammation; Neutrophils; Resolution of inflammation