Polysaccharides derived from Ganoderma lucidum fungus mycelia ameliorate indomethacin-induced small intestinal injury via induction of GM-CSF from macrophages

Cell Immunol. 2017 Oct:320:20-28. doi: 10.1016/j.cellimm.2017.08.001. Epub 2017 Aug 4.

Abstract

Non-steroidal anti-inflammatory drugs often cause ulcers in the human small intestine, but few effective agents exist to treat such injury. Ganoderma lucidum Karst, also known as "Reishi" or "Lingzhi", is a mushroom. We previously reported that a water-soluble extract from G. lucidum fungus mycelia (MAK) has anti-inflammatory effects in murine colitis induced by trinitrobenzene sulfonic acid, and induction of granulocyte macrophage colony-stimulating factor (GM-CSF) by MAK may provide anti-inflammatory effects. However, its effects on indomethacin-induced small intestinal injuries are unknown. The present study investigated the preventative effects of MAK via immunological function and the polysaccharides from MAK on indomethacin-induced ileitis in mice. Peritoneal macrophages (PMs) were stimulated in vitro with MAK and adoptively transferred to C57BL/6 mice intraperitoneally, which were then given indomethacin. Intestinal inflammation was evaluated after 24h. We performed in vivo antibody blockade to investigate the preventive role of GM-CSF, which derived from PMs stimulated with MAK. We then used PMs stimulated with MAK pre-treated by pectinase in an adoptive transfer assay to determine the preventive role of polysaccharides. Indomethacin-induced small intestinal injury was inhibited by adoptive transfer of PMs stimulated in vitro with MAK. In this transfer model, pre-treatment with anti-GM-CSF antibody but not with control antibody reversed the improvement of small intestinal inflammation by indomethacin. Pectinase pretreatment impaired the anti-inflammatory effect of MAK. PMs stimulated by MAK appear to contribute to the anti-inflammatory response through GM-CSF in small intestinal injury induced by indomethacin. The polysaccharides may be the components that elicit the anti-inflammatory effect.

Keywords: GM-CSF; Ganoderma lucidum; indomethacin; small intestine.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Cells, Cultured
  • Complex Mixtures / chemistry
  • Complex Mixtures / therapeutic use
  • Duodenal Ulcer / chemically induced
  • Duodenal Ulcer / immunology
  • Duodenal Ulcer / therapy*
  • Fungal Polysaccharides / isolation & purification
  • Fungal Polysaccharides / therapeutic use*
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Indomethacin / adverse effects*
  • Intestine, Small / drug effects*
  • Intestine, Small / immunology
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / transplantation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mycelium / chemistry
  • Polygalacturonase / chemistry
  • Reishi / chemistry*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Complex Mixtures
  • Fungal Polysaccharides
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Polygalacturonase
  • Indomethacin