Epithelial differentiation and energy production in ulcerative colitis

本研究的目的是研究LPS和促炎细胞因子在肠上皮细胞（IEC）中产生能量的潜力。LPS、IL-6、TNF-α刺激6 h后，ATP含量显著增加。氧消耗的时间性增强，这是完全由抗霉素A阻断，也被证明，表明LPS和促炎细胞因子调节IEC的能量代谢。这些灵活的能力，以产生能量似乎是相当必要的上皮功能在发炎mucosa.To建立上皮分化的标志物，碱性磷酸酶（ALP）的活性进行了研究。丁酸诱导的碱性磷酸酶活性与IEC 6细胞中的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与丁酸或视黄酸一起使用时，证实了ALP活性的协同诱导。其他生物活性物质如胞壁酰肽（MDP）或N-甲酰甲硫氨酰-赖氨酰-苯丙氨酸（FMLP）未能表现出进一步的诱导活性。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，这是已知的上皮分化相关标志物。

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.