Gut probiotic Lactobacillus rhamnosus attenuates PDE4B-mediated interleukin-6 induced by SARS-CoV-2 membrane glycoprotein.

Abstract

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.

• Authors: Minh Tan Pham, Albert Jackson Yang, Ming-Shan Kao, Uuganbayar Gankhuyag, Enkhbat Zayabaatar, Shiow-Lian Catherine Jin, Chun-Ming Huang
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 98 Pg. 108821 (12 2021) ISSN: 1873-4847 [Electronic] United States
• PMID: 34271099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Coronavirus M Proteins
• Ffar2 protein, mouse
• Interleukin-6
• Receptors, G-Protein-Coupled
• Butyric Acid
• Cyclic Nucleotide Phosphodiesterases, Type 4
• PDE4B protein, mouse

Topics

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