GMI, a fungal immunomodulatory protein, ameliorates SARS-CoV-2 envelope protein-induced inflammation in macrophages via inhibition of MAPK pathway.

Abstract

Clinically, COVID-19 is often accompanied by a severe immune response (cytokine storm) which produces a large number of cytokines, such as TNF-α, IL-6 and IL-12, and consequently causes acute respiratory distress syndrome (ARDS). GMI is a type of fungal immunomodulatory protein that is cloned from Ganoderma microsporum and acts as modulating immunocyte for various inflammatory diseases. This study identifies GMI as a potential anti-inflammatory agent and determines the effects of GMI on the inhibition of SARS-CoV-2-induced cytokine secretion. Functional studies showed that SARS-CoV-2 envelope (E) protein induces inflammatory process in murine macrophages RAW264.7 and MH-S cells and in phorbol 12-myristate 13-acetate (PMA)-stimulated human THP-1 cells. GMI exhibits a strong inhibitory effect for SARS-CoV-2-E-induced pro-inflammatory mediators, including NO, TNF-α, IL-6, and IL-12 in macrophages. GMI reduces SARS-CoV-2-E-induced intracellular inflammatory molecules, such as iNOS and COX-2, and inhibits SARS-CoV-2-E-stimulated phosphorylation of ERK1/2 and P38. GMI also downregulates pro-inflammatory cytokine levels in lung tissue and serum after the mice inhale SARS-CoV-2-E protein. In conclusion, this study shows that GMI acts as an agent to alleviate SARS-CoV-2-E-induced inflammation.

• Authors: Zhi-Hu Lin, Hsin Yeh, Hung-Chih Lo, Wei-Jyun Hua, Ming-Yang Ni, Li-Kai Wang, Ting-Ting Chang, Muh-Hwa Yang, Tung-Yi Lin
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 241 Pg. 124648 (Jun 30 2023) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 37119883 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Interleukin-6
• Tumor Necrosis Factor-alpha
• Cytokines
• Interleukin-12

Topics

• Humans
• Animals
• Mice
• SARS-CoV-2 (metabolism)
• COVID-19
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Inflammation
• Cytokines (metabolism)
• Macrophages (metabolism)
• Immunity
• Interleukin-12