| Author | Trentin, P. G. | |
| Author | Ferreira, T. P. T. | |
| Author | Arantes, A. C. S. | |
| Author | Ciambarella, B. T. | |
| Author | Cordeiro, R. S. B. | |
| Author | Flower, R. J. | |
| Author | Perreti, M. | |
| Author | Martins, M. A. | |
| Author | Silva, P. M. R. | |
| Access date | 2015-10-22T14:05:52Z | |
| Available date | 2016-02-01T06:30:06Z | |
| Document date | 2015 | |
| Citation | 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 | |
| Language | eng | pt_BR |
| Publisher | The British Pharmacological SOcity | pt_BR |
| Rights | open access | |
| Title | Annexin A1 mimetic peptide controls the inflammatory and fibrotic effects of silica particles in mice | pt_BR |
| Type | Article | |
| DOI | 10.1111/bph.13109 | |
| Abstract | 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 |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Queen Mary University of London. The William Harvey Research Institute. Department of Biochemical Pharmacology. London, UK. | pt_BR |
| Affilliation | Queen Mary University of London. The William Harvey Research Institute. Department of Biochemical Pharmacology. London, UK | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Annexin A1 | pt_BR |
| Subject | Mimetic peptide controls | pt_BR |
| Subject | Effects of silica particles | pt_BR |
| Subject | Mice | pt_BR |
| DeCS | Anexinas | pt_BR |
| DeCS | Peptídeos | pt_BR |
| DeCS | Dióxido de Silício | pt_BR |
| DeCS | Camundongos | pt_BR |
| Embargo date | 2016-01-31 | |
