Resveratrol protects mice against SEB‐induced acute lung injury and mortality by miR‐193a modulation that targets TGF‐β signalling

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‐β) 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‐β signalling (TGFβ2, TGFβR3) 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.

Protective effects of Δ9‐tetrahydrocannabinol against enterotoxin‐induced acute respiratory distress syndrome are mediated by modulation of microbiota

“…Lung tissues were also smashed using a Stomacher 80 Biomaster lab blender (Metrohm USA, Riverview, FL) in 10 ml of RPMI-1640 medium, lysed with Red Blood Lysing Buffer (Sigma-Aldrich, St. Louis, MO, USA) to remove red blood cells, washed with PBS, filtered and resuspended in PBS supplemented with 5% FCS. Then lungassociated mononuclear cells were isolated from lung cell suspensions in Ficoll-Histopaque ® -1077 (Sigma-Aldrich) at a 1:1 ratio under 350 g of centrifugation for 30 min, as described (Alghetaa et al, 2018). The lung-associated mononuclear cells were stored immediately in TRIzol reagent at −80 C freezer for RNA sequencing.…”

“…The portions of lung-associated mononuclear cells were used in the measurement of proton efflux rate. Also, broncho-alveolar lavage fluid (BALF) was collected from these euthanized mice according to the procedure described by Alghetaa et al (2018).…”

Resveratrol decreases CD45+CD206− subtype macrophages in LPS‐induced murine acute lung injury by SOCS3 signalling pathway

“…Resveratrol (Res), a phytoalexin antioxidant from red grapes, has anti‐inflammatory properties . Studies in vivo have confirmed that Res can attenuate the severity of ALI in animal models . Res or Res‐curcumin hybrids can significantly attenuate disease severity of ALI, accompanied with lower production of pro‐inflammatory cytokines and chemokines, such as TNF‐alpha, IL‐1beta, IL‐6, IL‐12, IL‐33, MIP‐2 and IL‐18.…”

“…7,8 Studies in vivo have confirmed that Res can attenuate the severity of ALI in animal models. 9,10 Res or Res-curcumin hybrids can significantly attenuate disease severity of ALI, accompanied with lower production of pro-inflammatory cytokines and chemokines, such as TNF-alpha, IL-1beta, IL-6, IL-12, IL-33, MIP-2 and IL-18. In contrast, the anti-inflammatory cytokines and molecular mediators, such as IL-10, heme oxygenase-1 (HO-1),Nrf2…”

Downregulation of long non-coding RNA nuclear enriched abundant transcript 1 promotes cell proliferation and inhibits cell apoptosis by targeting miR-193a in myocardial ischemia/reperfusion injury

“…, which is embedded in a CpG island, has been identified as a tumor suppressive miRNA in several cancers such as oral carcinoma, lung cancer and colorectal cancer [27][28][29][30][31][32][33]. Apart from cancers, it is disclosed that miR-193a is downregulated in intestinal inflammation in colitis, and upregulation of miR-193a promotes anti-inflammatory activities via targeting apoptotic pathways death receptor-6 (DR6) [34]. Hence, these previous evidences reveal that miR-193a influence cells activities in diverse diseases, thereby devoting to these disease developments and progressions, whereas few evidences of miR-193a in affecting I/R injury myocardial cells have been reported.…”