Effect of fatty acids on injury and repair of intestinal mucosal barrier

脂肪酸对肠粘膜屏障损伤与修复的影响

• 批准号: 12670531
• 负责人: SAITOH Osamu
• 金额: $ 0.96万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670531/
• 关键词: intestinal mucosa; intestinal epithelial cell; whole gut lavage fluid; barrier; permeability; fatty acid; Caco-2 cells; IL-8; K^+-channel; Caco-2細胞; T84細胞

1. Effect of fatty acids on chemokine production in intestinal epithelial cells, Caco-2 cellsButyrate, a short-chain fatty acid, decreased interleukin(IL)-8 production in intestinal epithelial cells, ω-3 fatty acids such as docosahexaenoic acid (DMA) and eicosapentaenoic acid (ERA) showed no effect on IL-8 production. Oleic acid (OA) and capric acid (CA) increased IL-8 production. Protein kinase C and phospholipase A2 were involved in signal transduction pathways for OA-induced IL-8 production but not for CA-induced IL-8 production.2. Measurement of proteins in whole gut lavage fluid (WGLF) and fecesEither WGLF or feces can be used as a sample to investigate pathophysiology and disease activity in patients with inflammatory bowel disease (IBD). In active IBD, the concentrations of granular proteins (lactoferrin, myeloperoxidase, PMN-elastase, lysozyme) were increased both in the supernatant and pellet. These findings suggested that although the migration of neutrophils into the lumen is extremely increased in active IBD, a number of neutrophils that migrated into the lumen did not release granular proteins. And lactoferrin is the most suitable of these proteins for use as a neutrophilderived WGLF marker of intestinal inflammation.3. Effects and cellular actions of oxidants on anion secretion in human colonic T84 cells.Oxidants potentiate both Ca^<2+>- and CAMP-stimulated Cl^- secretion by a direct effect on calcium-activated basolateral K^+ channel conductance, lowering its Ca^<2+> activation threshold. This effect may play an important role in amplifying and prolonging the secretory response of inflamed intestinal mucosa and enhancing the severity of diarrhea.

1.脂肪酸对肠上皮细胞、Caco-2细胞产生趋化因子的影响丁酸（一种短链脂肪酸）可降低肠上皮细胞产生白细胞介素（IL）-8，ω-3脂肪酸如二十二碳六烯酸（DMA）和二十碳五烯酸（ERA）对IL-8的产生无影响。油酸（OA）和癸酸（CA）增加IL-8的产生。蛋白激酶C和磷脂酶A2参与OA诱导IL-8产生的信号转导通路，但不参与CA诱导IL-8产生的信号转导通路.全肠灌洗液（WGLF）和粪便中蛋白质的测量WGLF或粪便均可用作研究炎症性肠病（IBD）患者的病理生理学和疾病活动的样本。在活动性IBD中，颗粒蛋白（乳铁蛋白、髓过氧化物酶、PMN弹性蛋白酶、溶菌酶）的浓度在上清液和沉淀中均增加。这些发现表明，虽然中性粒细胞迁移到管腔中的活动性IBD极大地增加，但迁移到管腔中的许多中性粒细胞并不释放颗粒蛋白。其中乳铁蛋白最适合作为肠道炎症的WGLF标志物.氧化剂对人结肠T84细胞阴离子分泌的影响和细胞作用氧化剂通过直接作用于钙激活的基底外侧K^+通道电导，降低其Ca^2+激活阈值，从而增强Ca^2+和cAMP刺激的Cl^-分泌。这种作用可能在放大和延长炎症肠粘膜的分泌反应和加重腹泻的严重程度中起重要作用。

项目成果

Sugi K., Saitoh O.: "Acute oxidant exposure of T84 intestinal cellspotentiate Ca^<2+>- and CAMP- dependent CI^- secretion"Digestion and Absorption. 23. 21-24 (2000)

Sugi K.，Saitoh O.：“T84肠细胞的急性氧化剂暴露增强Ca^2-和CAMP依赖性CI^-分泌”消化和吸收。

Teranish T, et al: "Nitric oxide increases the permeability of the Caco-2 cell monolayer in association with dephosphorylation of occludin"Bull Osaka Med College. 45. 11-19 (1999)

Teranish T 等人：“一氧化氮增加 Caco-2 细胞单层的通透性，与 occludin 的去磷酸化相关”Bull Osaka Med College。

Miyoshi H., Oka M., Sugi K., et al.: "Accuracy of detection of colorectal neoplasia using immunochemical occult blood test in symptomatic referred patients: comparison of retrospective and prospective studies"Internal Medicine. 39. 701-706 (2000)

Miyoshi H.、Oka M.、Sugi K.等人：“在有症状的转诊患者中使用免疫化学潜血试验检测结直肠肿瘤的准确性：回顾性和前瞻性研究的比较”内科。

Tanaka S, 他: "Medium-chain fntty acicts stimulate interleukor-8 production in Caw-2 cells with different mechanisms"J Gastroenternol Hepatol. 16. 748-754 (2001)

Tanaka S 等人：“中链脂肪酸以不同的机制刺激 Caw-2 细胞中白细胞介素 8 的产生”J Gastroenternol Hepatol。 16. 748-754 (2001)

Kayazawa M, et al.: "Lactoferrcn in whole gut lavoge fliuid or a marker for disease activity in inflammatory bowel disease"Am J Gastroenterol. 97. 360-369 (2002)

Kayazawa M 等人：“全肠灌洗液中的乳铁或炎症性肠病疾病活动的标记”Am J Gastroenterol。