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Annexin A1 mimetic peptide controls the inflammatory and fibrotic effects of silica particles in mice

Trentin, P G ; Ferreira, T P T ; Arantes, A C S ; Ciambarella, B T ; Cordeiro, R S B ; Flower, R J ; Perretti, M ; Martins, M A ; Silva, P M R

British journal of pharmacology, 2015-06, Vol.172 (12), p.3058-3071 [Periódico revisado por pares]

England: Blackwell Publishing Ltd

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Título:
Annexin A1 mimetic peptide controls the inflammatory and fibrotic effects of silica particles in mice
Autor: Trentin, P G ; Ferreira, T P T ; Arantes, A C S ; Ciambarella, B T ; Cordeiro, R S B ; Flower, R J ; Perretti, M ; Martins, M A ; Silva, P M R
Assuntos: Animals ; Annexin A1 - genetics ; Annexin A1 - pharmacology ; Chemokine CCL2 - metabolism ; Cytokines - metabolism ; Dexamethasone - pharmacology ; Disease Models, Animal ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Fibrosis - drug therapy ; Fibrosis - pathology ; Inflammation - drug therapy ; Inflammation - pathology ; Male ; Mice ; Mice, Knockout ; Peptides - pharmacology ; Research Papers ; Silicon Dioxide - toxicity ; Silicosis - drug therapy ; Silicosis - pathology
É parte de: British journal of pharmacology, 2015-06, Vol.172 (12), p.3058-3071
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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These authors contributed equally.
Descrição: Background and Purpose Endogenous glucocorticoids are pro‐resolving mediators, an example of which is the endogenous glucocorticoid‐regulated protein annexin A1 (ANXA1). Because silicosis is an occupational lung disease characterized by unabated inflammation and fibrosis, in this study we tested the therapeutic properties of the N‐terminal ANXA1‐derived peptide annexin 1‐(2‐26) (Ac2‐26) on experimental silicosis. Experimental Approach Swiss‐Webster mice were administered silica particles intranasally and were subsequently treated with intranasal peptide Ac2‐26 (200 μg per mouse) or dexamethasone (25 μg per mouse) for 7 days, starting 6 h post‐challenge. Ac2‐26 abolished the leukocyte infiltration, collagen deposition, granuloma formation and generation of pro‐inflammatory cytokines evoked by silica; these variables were only partially inhibited by dexamethasone. Key Results A clear exacerbation of the silica‐induced pathological changes was observed in ANXA1 knockout mice as compared with their wild‐type (WT) littermate controls. Incubation of lung fibroblasts from WT mice with Ac2‐26 in vitro reduced IL‐13 or TGF‐β‐induced production of CCL2 (MCP‐1) and collagen, but this peptide did not affect the production of CCL2 (MCP‐1) by stimulated fibroblasts from formyl peptide receptor type 1 (FPR1) knockout mice. Ac2‐26 also inhibited the production of CCL2 (MCP‐1) from fibroblasts of FPR2 knockout mice. Conclusions and Implications Collectively, our findings reveal novel protective properties of the ANXA1 derived peptide Ac2‐26 on the inflammatory and fibrotic responses induced by silica, and suggest that ANXA1 mimetic agents might be a promising strategy as innovative anti‐fibrotic approaches for the treatment of silicosis.
Editor: England: Blackwell Publishing Ltd
Idioma: Inglês

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Annexin A1 mimetic peptide controls the inflammatory and fibrotic effects of silica particles in mice

Trentin, P G ; Ferreira, T P T ; Arantes, A C S ; Ciambarella, B T ; Cordeiro, R S B ; Flower, R J ; Perretti, M ; Martins, M A ; Silva, P M R

England: Blackwell Publishing Ltd

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