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Autor | Trentin, P. G. | |
Autor | Ferreira, T. P. T. | |
Autor | Arantes, A. C. S. | |
Autor | Ciambarella, B. T. | |
Autor | Cordeiro, R. S. B. | |
Autor | Flower, R. J. | |
Autor | Perreti, M. | |
Autor | Martins, M. A. | |
Autor | Silva, P. M. R. | |
Fecha de acceso | 2015-10-22T14:05:52Z | |
Fecha de disponibilización | 2016-02-01T06:30:06Z | |
Fecha de publicación | 2015 | |
Referencia | TRENTIN, P. G. et al. Annexin A1 mimetic peptide controls the inflammatory and fibrotic effects of silica particles in mice. B British Journal of Pharmacology, v.172, p.3058–3071, 2015. | pt_BR |
ISSN | 1476-5381 | |
URI | https://www.arca.fiocruz.br/handle/icict/12041 | |
Idioma | eng | pt_BR |
Editor | The British Pharmacological SOcity | pt_BR |
Derechos de autor | open access | pt_BR |
Título | Annexin A1 mimetic peptide controls the inflammatory and fibrotic effects of silica particles in mice | pt_BR |
Tipo del documento | Article | pt_BR |
DOI | 10.1111/bph.13109 | |
Resumen en Inglés | 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. | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Afiliación | Queen Mary University of London. The William Harvey Research Institute. Department of Biochemical Pharmacology. London, UK. | pt_BR |
Afiliación | Queen Mary University of London. The William Harvey Research Institute. Department of Biochemical Pharmacology. London, UK | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Palavras clave en Inglês | Annexin A1 | pt_BR |
Palavras clave en Inglês | Mimetic peptide controls | pt_BR |
Palavras clave en Inglês | Effects of silica particles | pt_BR |
Palavras clave en Inglês | Mice | pt_BR |
DeCS | Anexinas | pt_BR |
DeCS | Peptídeos | pt_BR |
DeCS | Dióxido de Silício | pt_BR |
DeCS | Camundongos | pt_BR |
Fecha de embargo | 2016-01-31 |
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