Multiple anti-inflammatory pathways triggered by resveratrol lead to amelioration of staphylococcal enterotoxin B-induced lung injury.
OBJECTIVE
Inhalation of the superantigen,staphylococcal enterotoxin B (SEB), leads to the activation of the host T and invariant natural killer (iNK) T cells, thereby resulting in acute lung inflammation and respiratory failure but the underlying mechanism(s) of disease remain elusive, with limited treatment options. In this study, we investigated the therapeutic effectiveness of resveratrol, a plant polyphenol, during SEB-induced lung inflammation.


METHODS
C57BL/6 mice were exposed to SEB (50 µg·per mouse), administered intranasally, and were treated with resveratrol (100 mg·kg(-1)) before or after SEB exposure. Lung injury was studied by measuring vascular permeability, histopathological examination, nature of infiltrating cells, inflammatory cytokine induction in the bronchoalveolar fluid (BALF), apoptosis in SEB-activated T cells and regulation of SIRT1 and NF-κB signalling pathways.


RESULTS
Pretreatment and post-treatment with resveratrol significantly reduced SEB-induced pulmonary vascular permeability, and inflammation. Resveratrol significantly reduced lung infiltrating cells and attenuated the cytokine storm in SEB-exposed mice, which correlated with increased caspase-8-dependent apoptosis in SEB-activated T cells. Resveratrol treatment also markedly up-regulated Cd11b+ and Gr1+ myeloid-derived suppressor cells (MDSCs) that inhibited SEB-mediated T cell activation in vitro. In addition, resveratrol treatment was accompanied by up-regulation of SIRT1 and down-regulation of NF-κB in the inflammatory cells of the lungs.


CONCLUSIONS
The current study demonstrates that resveratrol may constitute a novel therapeutic modality to prevent and treat SEB-induced lung inflammation inasmuch because it acts through several pathways to reduce pulmonary inflammation.
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, USA.
Sadiye Amcaoglu
SA
Rieder
Prakash
P
Nagarkatti
Mitzi
M
Nagarkatti
D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis; D016207:Cytokines / Q000276:immunology; D042783:Endothelial Cells / Q000187:drug effects; D004768:Enterotoxins / Q000008:administration & dosage*; D005260:Female; D008168:Lung / Q000166:cytology / Q000276:immunology; D055370:Lung Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013267:Stilbenes / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D051996:Transcription Factor RelA / Q000276:immunology
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004768:Enterotoxins; D013267:Stilbenes; D051996:Transcription Factor RelA; C031818:enterotoxin B, staphylococcal; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol