Resveratrol protects mice against SEB-induced acute lung injury and mortality by miR-193a modulation that targets TGF-ß signalling.
J Cell Mol Med
; 22(5): 2644-2655, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29512867
ABSTRACT
Staphylococcal enterotoxin B (SEB) is a potent superantigen produced by Staphylococcus aureus that triggers a strong immune response, characterized by cytokine storm, multi-organ failure, and often death. When inhaled, SEB can cause acute lung injury (ALI) and respiratory failure. In this study, we investigated the effect of resveratrol (RES), a phytoallexin, on SEB-driven ALI and mortality in mice. We used a dual-exposure model of SEB in C3H/HeJ mice, which caused 100% mortality within the first 5 days of exposure, and treatment with RES resulted in 100% survival of these mice up to 10 days post-SEB exposure. RES reduced the inflammatory cytokines in the serum and lungs, as well as T cell infiltration into the lungs caused by SEB. Treatment with RES also caused increased production of transforming growth factor-beta (TGF-ß) in the blood and lungs. RES altered the miRNA profile in the immune cells isolated from the lungs. Of these, miR-193a was strongly induced by SEB and was down-regulated by RES treatment. Furthermore, transfection studies and pathway analyses revealed that miR-193a targeted several molecules involved in TGF-ß signalling (TGFß2, TGFßR3) and activation of apoptotic pathways death receptor-6 (DR6). Together, our studies suggest that RES can effectively neutralize SEB-mediated lung injury and mortality through potential regulation of miRNA that promote anti-inflammatory activities.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Fator de Crescimento Transformador beta
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Substâncias Protetoras
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MicroRNAs
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Lesão Pulmonar Aguda
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Resveratrol
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article