The inhibitory effect of oral administration of lentinan on DSS-induced inflammation is exerted by the migration of T cells activated in the ileum to the colon

Eur J Pharmacol. 2023 May 5:946:175631. doi: 10.1016/j.ejphar.2023.175631. Epub 2023 Feb 28.

Abstract

Oral administration of lentinan ameliorated dextran sulfate sodium (DSS)-induced colitis through Dectin-1 receptor on intestinal epithelial cells. However, it is unclear where lentinan affects in the intestine to prevent the inflammation. We found that the administration of lentinan has induced migration of CD4+ cells from the ileum to the colon by using Kikume Green-Red (KikGR) mice in this study. This result suggests that the oral lentinan treatment could accelerate the migration of Th cells in lymphocyte from ileum into the colon during lentinan intake. Then, C57BL/6 mice were administered 2% DSS to induce colitis. The mice were administered lentinan daily via oral or rectal route before DSS administration. Its rectal administration also suppressed DSS-induced colitis, but its suppressive effects were lower compared to when orally administered, indicating that the biological responses to lentinan in the small intestine contributed to the anti-inflammatory effects. In normal mice (without DSS treatment), the expression of Il12b was significantly increased in the ileum by the oral administration of lentinan, but not by rectal one. On the other hand, no change was observed in the colon by either administration method. In addition, Tbx21 was significantly increased in the ileum. These suggested that IL-12 was increased in the ileum and Th1 cells differentiated in dependence on it. Therefore, Th1 predominant condition in the ileum could influence immunity in the colon and improve the colitis.

Keywords: DSS-Induced colitis; Inflammatory bowel disease; Intestinal immunity; Kikume green-red (KikGR) mice; Lentinan; Lentinula edodes.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colon
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Ileum
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Lentinan* / administration & dosage
  • Lentinan* / adverse effects
  • Mice
  • Mice, Inbred C57BL
  • Th1 Cells

Substances

  • Dextran Sulfate
  • Lentinan
  • Antineoplastic Agents