title: Modulation of chemokine expression on intestinal epithelial cells by Kampo (traditional Japanese herbal) medicine, Hochuekkito, and its active ingredients.
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.
authors.affiliation: Graduate School of Infection Control Sciences, Kitasato University, Tokyo, 108-8641, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Sekiya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kiyohara
authors.forename: Hiroko
authors.initials: H
authors.lastname: Maruyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yabe
authors.forename: Haruki
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D054413:Chemokine CCL11 / Q000378:metabolism; D054418:Chemokine CCL20 / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D020835:Medicine, Kampo; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010581:Peyer's Patches / Q000187:drug effects / Q000378:metabolism; D008517:Phytotherapy; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C515458:Ccl11 protein, rat; C486997:Ccl20 protein, rat; C491541:Ccl25 protein, mouse; C575676:Ccl25 protein, rat; D054413:Chemokine CCL11; D054418:Chemokine CCL20; D018925:Chemokines; D019742:Chemokines, CC; D004365:Drugs, Chinese Herbal; C496454:Fgf7 protein, mouse; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C402943:bu-zhong-yi-qi-tang; D051523:Fibroblast Growth Factor 7