Modulation of chemokine expression on intestinal epithelial cells by Kampo (traditional Japanese herbal) medicine, Hochuekkito, and its active ingredients

J Nat Med. 2013 Jul;67(3):626-35. doi: 10.1007/s11418-012-0724-1. Epub 2012 Dec 1.

Abstract

The intestinal epithelial cells sit at the interface between a lumen and a lamina propria or lymph nodes such as Peyer's patches, where they play important roles in maintaining intestinal homeostasis through chemokine secretion. This study investigated the effect of Hochuekkito (TJ-41)-a traditional Japanese herbal (Kampo) formula used as a tonic for weakness-on chemokine expression in intestinal epithelial cells in order to explore the mechanism of its modulating effect against mucosal immunity. When cells from the rat normal small intestinal epithelial cell-line IEC-6 were stimulated with TJ-41, mRNA expression of CC chemokine ligand (CCL) 11 (eotaxin), CCL20 (MIP-3α) and CCL25 (TECK) was enhanced. Oral administration of TJ-41 to methotrexate-treated mice enhanced mRNA expression of CCL25 and keratinocyte growth factor in the jejunum with, decreasing mRNA expression of the inflammatory marker tumor necrosis factor (TNF)-α. Although oral administration of TJ-41 did not affect CCL20 mRNA expression in villus epithelium of methotrexate-treated mice, enhancement of CCL20 mRNA expression was observed in Peyer's patches. Immunohistochemical analysis detected dense staining with anti-CCL20 antibody in the follicle-associated epithelium region of Peyer's patches in mice administered TJ-41. Analysis of active ingredients indicates that polysaccharide-containing macromolecules in TJ-41 contribute to the enhancement of CCL20 mRNA expression through an intracellular signal cascade via nuclear factor kappa B (NF-κB) activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Chemokine CCL11 / metabolism
  • Chemokine CCL20 / metabolism
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Chemokines, CC / metabolism
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Female
  • Fibroblast Growth Factor 7 / metabolism
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Jejunum / drug effects*
  • Jejunum / immunology
  • Jejunum / metabolism
  • Medicine, Kampo*
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Peyer's Patches / drug effects
  • Peyer's Patches / metabolism
  • Phytotherapy
  • Plants, Medicinal
  • RNA, Messenger / metabolism
  • Rats
  • Signal Transduction
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Ccl11 protein, rat
  • Ccl20 protein, rat
  • Ccl25 protein, mouse
  • Ccl25 protein, rat
  • Chemokine CCL11
  • Chemokine CCL20
  • Chemokines
  • Chemokines, CC
  • Drugs, Chinese Herbal
  • Fgf7 protein, mouse
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • bu-zhong-yi-qi-tang
  • Fibroblast Growth Factor 7