Resveratrol attenuates staphylococcal enterotoxin B-activated immune cell metabolism via upregulation of miR-100 and suppression of mTOR signaling pathway

Frontiers in Pharmacology

Pharmacology

Nagireddy Putluri¹  Goushuai Cai²  Kiesha Wilson³  Mitzi Nagarkatti³  Narendra Singh³  Prakash Nagarkatti³  Amira Mohammed⁴  Hasan Alghetaa⁴ 

[1] Dan L. Duncan Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, United States;Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States;Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States;Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq;

关键词: MiR-100;    ARDS (acute respiratory disease syndrome);    T-cell metabolism;    mTOR;    staphylococcal enterotoxin B (SEB);    resveratrol;    metabolome;    ScRNA;   

DOI  :  10.3389/fphar.2023.1106733

 received in 2022-11-24, accepted in 2023-02-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. Also, Single-cell RNA-seq (scRNA seq) unveiled the decreased expression of mTOR in a variety of immune cells in the lungs. There was also an increase in glycolytic and mitochondrial respiration in the cells from SEB + VEH group in comparison with SEB + RES group. Together these data suggested that RES alters the metabolic reprogramming of SEB-activated immune cells, through suppression of mTOR activation and its down- and upstream effects on energy metabolism. Also, miR-100 could serve as novel potential therapeutic molecule in the amelioration of ARDS.

【 授权许可】

Unknown   
Copyright © 2023 Alghetaa, Mohammed, Singh, Wilson, Cai, Putluri, Nagarkatti and Nagarkatti.