Immunomodulatory activity of Ganoderma lucidum immunomodulatory protein via PI3K/Akt and MAPK signaling pathways in RAW264.7 cells.

Ganoderma lucidum immunomodulatory protein (FIP‐glu) is an active ingredient with potential immunoregulatory functions. The study was conducted to explore the immunomodulatory activities of recombinant FIP‐glu (rFIP‐glu) and its possible mechanism in macrophage RAW264.7 cells. In vitro assays of biological activity indicated that rFIP‐glu significantly activated RAW264.7 cells and possessed proinflammatory and anti‐inflammatory abilities. RNA sequencing analysis and Western blot analysis showed that macrophage activation involved PI3K/Akt and MAPK pathways. Furthermore, real‐time quantitative polymerase chain reaction indicated that the PI3K inhibitor LY294002 blocked the messenger RNA (mRNA) levels of MCP‐1 (CCL‐2), the MEK1/2 inhibitor U0126 reduced the mRNA levels of TNF‐α and MCP‐1 (CCL‐2), and the JNK1/2/3 inhibitor SP600125 prevented the upregulation of inducible nitric oxide synthase mRNA in rFIP‐glu‐induced cells. rFIP‐glu did not mediate these inflammatory effects through a general pathway but rather through a different pathway for a different inflammatory mediator. These data imply that rFIP‐glu possessed immunomodulatory activity in macrophages, which was mediated through PI3K/Akt and MAPK pathways. [ABSTRACT FROM AUTHOR]