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

J Cell Physiol. 2019 Dec;234(12):23337-23348. doi: 10.1002/jcp.28901. Epub 2019 May 30.

Abstract

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.

Keywords: RAW 264.7 cells; macrophage activation; mitogen-activated protein kinases; phosphatidylinositol 3-kinases; sequence analysis, RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fungal Proteins / pharmacology*
  • Immunomodulation / drug effects
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / physiology
  • Macrophage Activation / drug effects
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Phosphatidylinositol 3-Kinases / drug effects*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / drug effects*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RAW 264.7 Cells
  • Reishi*

Substances

  • Fungal Proteins
  • Proto-Oncogene Proteins c-akt