4.6 Article

Dual Effect of the Extract from the Fungus Coriolus versicolor on Lipopolysaccharide-Induced Cytokine Production in RAW 264.7 Macrophages Depending on the Lipopolysaccharide Concentration

期刊

JOURNAL OF INFLAMMATION RESEARCH
卷 15, 期 -, 页码 3599-3611

出版社

DOVE MEDICAL PRESS LTD
DOI: 10.2147/JIR.S364945

关键词

Coriolus versicolor; pro-inflammatory cytokines; Toll-like receptor 4; phosphorylated I kappa B; phosphatidylinositol 3-kinase; CD14 glycoprotein

资金

  1. Polish Minister of Science and Higher Education [008/RID/2018/19]

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This study investigated the effects of extract from Coriolus versicolor on the production of pro-inflammatory cytokines in macrophages. The results showed that the extract can stimulate the secretion of IL-6 and TNF-α, and alter the expression of related signaling pathway components. The effects of the extract on cytokine production can be antagonistic or additive depending on the concentration of LPS.
Purpose: Extract from the fungus Coriolus versicolor (CV) is classified as an immunological response modifier. Previously, we have shown that this extract induces interleukin 6 (IL-6)-related extension of lipopolysaccharide (LPS)-induced fever. This study investigated the effect of CV extract on the production of pro-inflammatory cytokines and the expression of components of signal transduction pathways leading to the secretion of cytokines from RAW 264.7 macrophages stimulated with different doses of LPS. Methods: RAW 264.7 cells were stimulated with CV extract alone or co-treated with CV extract and LPS. The level of IL-6 and tumour necrosis factor alpha (TNF-alpha) in the culture media was measured using ELISA. Protein expression of Toll-like receptor (TLR) 4, phosphorylated I kappa B (p-I kappa B), CD14 glycoprotein and phospho-phosphatidylinositol 3-kinase (p-PI3K) was evaluated using Western blot. The effects of TLR4, nuclear factor kappa B (NF-kappa B) and p-PI3K on cytokine secretion were estimated using inhibitors: TAK-242, JSH-23 and LY294002. Results: CV extract itself stimulates the secretion of IL-6 and TNF-alpha and increases the expression of TLR4, p-I kappa B and p-PI3K. The presence of CV extract during the treatment of cells with lower concentrations of LPS (10 and 100 ng/mL) increases the cytokine production. Co-stimulation of cells with CV extract and LPS at a higher dose (500 ng/mL) decreases the secretion of cytokines. This effect is related to the changes in the expression of TLR4, CD14 glycoprotein, p-I kappa B and p-PI3K. Conclusion: This is the first report showing that the CV extract-induced production of cytokines is mediated by the PI3K signalling pathway. This extract acts antagonistically or additively with LPS on the production of IL-6 and TNF-alpha, depending on the LPS concentration. Our results are helpful for illustrating the mechanisms for the immunostimulatory effect of CV extract in inflammatory processes.

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