Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Program in Molecular Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Int J Biol Macromol. 2023 Jun 30;241:124648. doi: 10.1016/j.ijbiomac.2023.124648. Epub 2023 Apr 28.
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.
临床上，COVID-19 常伴有严重的免疫反应（细胞因子风暴），产生大量细胞因子，如 TNF-α、IL-6 和 IL-12，进而导致急性呼吸窘迫综合征（ARDS）。GMI 是一种从灵芝中克隆的真菌免疫调节蛋白，作为免疫细胞调节剂，用于各种炎症性疾病。本研究将 GMI 鉴定为一种潜在的抗炎剂，并确定 GMI 对抑制 SARS-CoV-2 诱导的细胞因子分泌的影响。功能研究表明，SARS-CoV-2 包膜（E）蛋白在鼠源巨噬细胞 RAW264.7 和 MH-S 细胞以及佛波醇 12-肉豆蔻酸 13-醋酸盐（PMA）刺激的人 THP-1 细胞中诱导炎症过程。GMI 对 SARS-CoV-2-E 诱导的促炎介质（包括巨噬细胞中的 NO、TNF-α、IL-6 和 IL-12）表现出强烈的抑制作用。GMI 降低了 SARS-CoV-2-E 诱导的细胞内炎症分子，如 iNOS 和 COX-2，并抑制了 SARS-CoV-2-E 刺激的 ERK1/2 和 P38 的磷酸化。GMI 还下调了 SARS-CoV-2-E 蛋白吸入后小鼠肺组织和血清中的促炎细胞因子水平。总之，本研究表明，GMI 作为一种减轻 SARS-CoV-2-E 诱导炎症的药物发挥作用。
