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Inflamm Res ; 73(6): 1019-1031, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38656426

RESUMO

OBJECTIVE: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge. METHODS: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed. RESULTS: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4+Foxp3+, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation. CONCLUSION: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.


Assuntos
Angiotensina I , Lipopolissacarídeos , Pulmão , Ovalbumina , Fragmentos de Peptídeos , Animais , Angiotensina I/uso terapêutico , Angiotensina I/farmacologia , Angiotensina I/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/uso terapêutico , Fragmentos de Peptídeos/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/imunologia , Ovalbumina/imunologia , Camundongos , Masculino , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Camundongos Endogâmicos BALB C , Inflamação/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Eosinofilia/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologia
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