Annexin A1 mimetic peptide controls the inflammatory and fibrotic effects of silica particles in mice
2015
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.
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