Immunomodulatory Activity of Ganoderma atrum Polysaccharide on Purified T Lymphocytes through Ca2+/CaN and Mitogen-Activated Protein Kinase Pathway Based on RNA Sequencing

J Agric Food Chem. 2017 Jul 5;65(26):5306-5315. doi: 10.1021/acs.jafc.7b01763. Epub 2017 Jun 26.

Abstract

Our previous study has demonstrated that Ganoderma atrum polysaccharide (PSG-1) has immunomodulatory activity on spleen lymphocytes. However, how PSG-1 exerts its effect on purified lymphocytes is still obscure. Thus, this study aimed to investigate the immunomodulatory activity of PSG-1 on purified T lymphocytes and further elucidate the underlying mechanism based on RNA sequencing (RNA-seq). Our results showed that PSG-1 promoted T lymphocytes proliferation and increased the production of IL-2, IFN-γ, and IL-12. Meanwhile, RNA-seq analysis found 394 differentially expressed genes. KEGG pathway analysis identified 20 significant canonical pathways and seven biological functions. Furthermore, PSG-1 elevated intracellular Ca2+ concentration and calcineurin (CaN) activity and raised the p-ERK, p-JNK, and p-p38 expression levels. T lymphocytes proliferation and the production of IL-2, IFN-γ, and IL-12 were decreased by the inhibitors of calcium channel and mitogen-activated protein kinases (MAPKs). These results indicated that PSG-1 possesses immunomodulatory activity on purified T lymphocytes, in which Ca2+/CaN and MAPK pathways play essential roles.

Keywords: Ca2+/CaN pathway; Ganoderma atrum polysaccharide; MAPK pathway; RNA-seq; purified T lymphocytes.

MeSH terms

  • Calcineurin / genetics
  • Calcineurin / immunology*
  • Calcium / immunology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Ganoderma / chemistry*
  • Immunologic Factors / pharmacology*
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / immunology
  • Plant Extracts / pharmacology*
  • Polysaccharides / pharmacology*
  • Sequence Analysis, RNA
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Vegetables / chemistry*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / immunology

Substances

  • Immunologic Factors
  • Interleukin-2
  • Plant Extracts
  • Polysaccharides
  • Interleukin-12
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • Calcineurin
  • Calcium