Modulation of chemokine expression on intestinal epithelial cells by Kampo (traditional Japanese herbal) medicine, Hochuekkito,and its active ingredients
Modulation of chemokine expression on intestinal epithelial cells by Kampo (traditional Japanese herbal) medicine, Hochuekkito,and its active ingredients
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汉方药 Hochuekkito 及其活性成分对肠上皮细胞趋化因子表达的调节
DOI：
10.1007/s11418-012-0724-1
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发表时间：
2012
影响因子：
3.3
通讯作者：
Haruki Yamada
中科院分区：
文献类型：
--
作者：
Michiko Sekiya;Hiroaki Kiyohara;Hiroko Maruyama;Takeshi Yabe;Haruki Yamada
肠上皮细胞位于管腔和固有层或淋巴结（如派尔氏淋巴结）之间的界面，它们通过趋化因子分泌在维持肠道稳态方面发挥着重要作用。本研究调查了 Hochuekkito (TJ-41)（一种用于补虚的日本传统草药（汉方）配方）对肠上皮细胞趋化因子表达的影响，以探讨其调节粘膜免疫作用的机制。当用 TJ-41 刺激大鼠正常小肠上皮细胞系 IEC-6 的细胞时，CC 趋化因子配体 (CCL) 11（eotaxin）、CCL20 (MIP-3α) 和 CCL25 (TECK) 的 mRNA 表达增强。给甲氨蝶呤治疗的小鼠口服 TJ-41 可以增强空肠中 CCL25 和角质形成细胞生长因子的 mRNA 表达，同时降低炎症标志物肿瘤坏死因子 (TNF)-α 的 mRNA 表达。尽管口服 TJ-41 并不影响甲氨蝶呤治疗小鼠绒毛上皮中 CCL20 mRNA 的表达，但在派尔氏淋巴结中观察到 CCL20 mRNA 表达的增强。免疫组织化学分析检测到给予 TJ-41 的小鼠派尔氏集结的滤泡相关上皮区域存在抗 CCL20 抗体的密集染色。活性成分分析表明，TJ-41 中的含多糖大分子有助于通过核因子 kappa B (NF-κB) 激活的细胞内信号级联增强 CCL20 mRNA 表达。
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.