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J Nutr Biochem ; 98: 108821, 2021 12.
Article in English | MEDLINE | ID: covidwho-1309296


Membrane glycoprotein is the most abundant protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but its role in coronavirus disease 2019 (COVID-19) has not been fully characterized. Mice intranasally inoculated with membrane glycoprotein substantially increased the interleukin (IL)-6, a hallmark of the cytokine storm, in bronchoalveolar lavage fluid (BALF), compared to mice inoculated with green fluorescent protein (GFP). The high level of IL-6 induced by membrane glycoprotein was significantly diminished in phosphodiesterase 4 (PDE4B) knockout mice, demonstrating the essential role of PDE4B in IL-6 signaling. Mycelium fermentation of Lactobacillus rhamnosus (L. rhamnosus) EH8 strain yielded butyric acid, which can down-regulate the PDE4B expression and IL-6 secretion in macrophages. Feeding mice with mycelia increased the relative abundance of commensal L. rhamnosus. Two-week supplementation of mice with L. rhamnosus plus mycelia considerably decreased membrane glycoprotein-induced PDE4B expression and IL-6 secretion. The probiotic activity of L. rhamnosus plus mycelia against membrane glycoprotein was abolished in mice treated with GLPG-0974, an antagonist of free fatty acid receptor 2 (Ffar2). Activation of Ffar2 in the gut-lung axis for down-regulation of the PDE4B-IL-6 signalling may provide targets for development of modalities including probiotics for treatment of the cytokine storm in COVID-19.

Coronavirus M Proteins/pharmacology , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Interleukin-6/metabolism , Lacticaseibacillus rhamnosus/physiology , Probiotics/pharmacology , SARS-CoV-2/metabolism , Animals , Butyric Acid , Cell Line , Cloning, Molecular , Cyclic Nucleotide Phosphodiesterases, Type 4/genetics , Female , Fermentation , Gene Expression Regulation/drug effects , Humans , Interleukin-6/genetics , Mice , Mice, Inbred ICR , Receptors, G-Protein-Coupled/metabolism