Andersson David, Kotarsky Knut, Wu Jun, Agace William, Duan Rui-Dong
Gastroenterology Laboratory, Institution of Clinical Science, Biomedical Center, B11, Lund University, 22184, Lund, Sweden.
Dig Dis Sci. 2009 Jul;54(7):1440-8. doi: 10.1007/s10620-008-0509-2. Epub 2008 Nov 7.
Alkaline sphingomyelinase (Alk-SMase) is a key enzyme in the intestinal tract for digestion of dietary sphingomyelin (SM), which generates lipid messengers with cell-cycle regulating effects. The enzyme is significantly decreased in ulcerative colitis and colon cancer. Based on this information, we wanted to investigate whether the enzyme had preventive effects against murine colitis. We report herein a method to express a biologically active Alk-SMase from Pichia pastoris yeast cells. By using the expressed enzyme to treat a rat colitis model induced by dextran sulfate sodium, we found that intrarectal instillation of Alk-SMase once daily for 1 week significantly reduced the inflammation score and protected the colonic epithelium from inflammatory destruction. We found a tendency for decreased tumor necrosis factor (TNF)-alpha expression in the Alk-SMase-treated group. This study, for the first time, provides a method to produce the enzyme and shows the potential applicability of the enzyme in the treatment of inflammatory bowel diseases.
碱性鞘磷脂酶（Alk-SMase）是肠道中消化膳食鞘磷脂（SM）的关键酶，其可生成具有细胞周期调节作用的脂质信使。该酶在溃疡性结肠炎和结肠癌中显著减少。基于此信息，我们想研究该酶是否对小鼠结肠炎具有预防作用。我们在此报告一种从毕赤酵母细胞中表达具有生物活性的Alk-SMase的方法。通过使用表达的酶治疗由葡聚糖硫酸钠诱导的大鼠结肠炎模型，我们发现每天一次直肠内滴注Alk-SMase，持续1周，可显著降低炎症评分，并保护结肠上皮免受炎症破坏。我们发现Alk-SMase治疗组中肿瘤坏死因子（TNF）-α表达有降低的趋势。本研究首次提供了一种生产该酶的方法，并显示了该酶在治疗炎症性肠病中的潜在适用性。
