Butyrate mediates the amelioration of Staphylococcal Enterotoxin B-induced Acute Respiratory Distress Syndrome by downregulating the expression of Histone Deacetylases

Autor: Muthanna Ali Sultan, Prakash Nagarkatti, Mitzi Nagarkatti
Rok vydání: 2021
Předmět:
Zdroj: The Journal of Immunology. 206:13.12-13.12
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.206.supp.13.12
Popis: Despite rigorous global containment and quarantine efforts that have been applied globally to control SARS-CoV-2, the spreading of this contagious disease has accelerated all over the world. In our study, we used staphylococcal enterotoxin B (SEB), which is a superantigen can lead to toxic shock syndrome in C57BL/6 murine model and thus, mimics COVID19. In the current study, we investigated the suppressive effect of sodium butyrate (BUT) on a murine model of SEB-induced Acute Respiratory Distress Syndrome (ARDS). The data shows that supplementation with BUT at a dose of 200 mg/kg orally reduced overall ARDS severity. Plethysmography analysis data indicated that sodium butyrate improves the clinical functions of the lungs. In addition, our flow cytometry data indicated that BUT mediated the suppression of lung mononuclear cells such as CD4+ T cells, CD8+ T cells, VB8+ T cells and NK-T cells while at the same time increasing T regulatory cells. Cytokine storm is one of the most important challenge in COVID19 cases, in our study, we have found that the proinflammatory cytokines such as IL-2, TNFα and IFNγ in broncho-alveolar lavage fluid (BALF) significantly decreased in SEB+BUT compared to SEB+VEH as detected by ELISA. Additionally, histopathological analysis of H & E stained lungs indicated that BUT decreased the level of infiltration of inflammatory cells in the lungs of SEB+BUT compared to SEB+VEH mice. Additionally, we investigated the role of BUT on the expression of histone deacetylases (HDACs). Collectively, our data suggested that BUT ameliorated SEB-induced ARDS by downregulating the expression of class I and Class II HDACs which mediate the increase in T regulatory cells that suppress the inflammatory response in SEB-induced ARDS.
Databáze: OpenAIRE
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