期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 22, 期 5, 页码 2644-2655出版社
WILEY
DOI: 10.1111/jcmm.13542
关键词
3,4,5-trihydroxy-trans-stilbene; acute lung injury; death receptor 6; microRNA (miRNA/miR); miR-193; pulmonary disease; resveratrol; staphylococcal enterotoxin B; transforming growth factor-beta
资金
- NIH [P01AT003961, R01AT006888, R01MH094755, P20GM103641, R01AI129788, R01AI123947]
- National Center for Complementary & Integrative Health [K01AT007824, R01AT006888, P01AT003961] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI123947, R01AI129788] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM103641] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH094755] Funding Source: NIH RePORTER
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-beta) 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-beta signalling (TGF beta 2, TGF beta R3) 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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