Epithelial differentiation and energy production in ulcerative colitis

溃疡性结肠炎的上皮分化和能量产生

• 批准号: 08671405
• 负责人: FUKUSHIMA Kouhei
• 金额: $ 1.34万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671405/
• 关键词: inflammatory bowel disease; ulcerative colitis; epithelial cell; differentiation; cytokine; alkaline phosphatase; アルカリフォスファターゼ; 上皮細胞; エネルギー; butyrate

The purpose of the present study is to investigate potential of LPS and proinflammatory cytokines for energy production in intestinal pithelial cells (IEC). When the cells were stimulated by LPS,IL-6 or TNF-a, ATP amount significantly increased after 6 hours. Chronological enhancement of oxgen consumption, which was completely blocked by antimycin A,was also demonstrated, indicating that LPS and proinflammatory cytokines modulate energy metabolism of IEC.These flexible capacities to generate energy appear to be quite essential for epithelial functions in inflamed mucosa.To establish markers for epithelial differentiation, the activity of alkaline phosphatase (ALP) was investigated. Butyrate-induced alkaline phosphatase activity is closely associated with differentiation-like phenomena in IEC6 cells, although the type of isoenzyme and cellular localization of the activity are different from those observed in mucosa. When LPS was additionally used with butyrate or retinoic acid, synergistic induction of ALP activities was demonstrated. Other bioactive chemicals such as muramyl peptides (MDP) or N-formylmethionyl-leycyl-phenylalanine (FMLP) failed to exhibit further induction of the activities. The present study clearly demonstrated that the specific combination of bacterial products synergistically modulated ALP activity of intestinal epithelial cells, which is known to be an epithelial differentiation-associated marker.

本研究的目的是探讨LPS和促炎细胞因子在肠上皮细胞（IEC）能量产生中的潜力。当LPS、IL-6或TNF-a刺激细胞时，6小时后ATP量显著增加。研究还证实，抗霉素A完全阻断了氧消耗的时序增强，这表明LPS和促炎细胞因子调节了IEC的能量代谢。这些产生能量的灵活能力似乎对炎症粘膜的上皮功能至关重要。为了建立上皮分化的标志物，研究了碱性磷酸酶（ALP）的活性。在IEC6细胞中，丁酸盐诱导的碱性磷酸酶活性与分化样现象密切相关，尽管同工酶的类型和活性的细胞定位与在粘膜中观察到的不同。当LPS与丁酸盐或维甲酸一起使用时，ALP活性被证明是协同诱导的。其他生物活性化学物质如muramyl peptide （MDP）或N-formylmethionyl-leycyl-phenylalanine （FMLP）不能进一步诱导活性。本研究清楚地表明，细菌产物的特定组合协同调节肠上皮细胞的ALP活性，这是一种已知的上皮分化相关标志物。

项目成果

福島 浩平: "Sodium bufyrate-induced liver-type alkaline activity in a small intestinal call lire,IEC6" Digestive Digease and Scieuce. (in press).

Kohei Fukushima：“丁酸钠在小肠中诱导肝型碱性活性，IEC6”消化消化酶和科学（正在出版）。

福島浩平: "Lipopoly saccharide exhibits synergistic Inhance ment of butyrate induced-and retinocc acid mediated- alkaline phosphatase activity on small intectinat cell line" Digestion. (in press).

Kohei Fukushima：“脂多糖在小 intectinat 细胞系上表现出丁酸诱导和视黄酸介导的碱性磷酸酶活性的协同增强”消化（正在出版）。

福島 浩平: "かなえ医学助成金.受賞者研究業績集 第24集 大腸全摘後の残存小腸上皮の適応と促進するための基礎的検討" かなえ医学振興財団, 400(うち23ページ) (1997)

福岛航平：“佳苗医疗补助金获奖者研究成果第 24 卷，全结肠切除术后残留小肠上皮的适应和促进的基础研究”，佳苗医学基金会，400（23 页）（1997 年）

K. Fukushima et. al.: "Energy Production induced by lipopolysaccharide (LPS) and prainflammatory cytokines in intestinal epithelial cells" Gastroenterology. 110. -A911 (1996)

K.福岛等。