Grant-in-Aid for Scientific Research (C).
|Research Institution||Osaka Medical College|
SAITOH Osamu Osaka Medical College, Internal Medicine, associate, 医学部, 講師 (40186929)
小島 敬史 大阪医科大学, 医学部, 専攻医
杉 和憲 大阪医科大学, 医学部, 助手
NAKAGAWA Ken Osaka Medical College, Internal Medicine, staff, 医学部, 助手 (00278532)
萱澤 正伸 大阪医科大学, 医学部, 専攻医
田中 正剛 大阪医科大学, 医学部, 専攻医
KOJIMA Keishi Osaka Medical College, Internal Medicine, fellow
SUGI Kazunori Osaka Medical College, Internal Medicine, staff
KAYAZAWA Masanobu Osaka Medical College, Internal Medicine, fellow
TANAKA Seigou Osaka Medical College, Internal Medicine, fellow
|Project Fiscal Year
1998 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1999 : ¥500,000 (Direct Cost : ¥500,000)
|Keywords||intestinal mucosa / intestinal epithelial cell / permeability / barrier / nitric oxide / fatty acid / Caco-2 cells / IL-8 / 腸粘膜 / 腸上皮細胞 / 透過性 / バリヤー機構 / 脂肪酸 / Caco-2細胞|
1. Effect of nitric oxide (NO) on intestinal epithelial permeability and tight junction protein (occludin)
NO donors increased the permeability of the Caco-2 cell monolayer. NOS inhibitors suppressed taurocholate-induced hyperpermeability. In the presence of NO donor, fluorescence was observed at the paracellular space one hour after the addition of FITC-dextran to the apical compartment. In the presence of NO donor, the higher molecular-weight band of occludin became faint. In the presence of NO donor, bands obtained using anti-phophoserine antibody corresponding with the higher molecular-weight band of occuludin became faint. In the presence of NO donor, occludin was stained at the tight junction but the stain was a little broader than that in the control. These findings suggested that intestinal epithelial permeability is increased not only by exogenously administered NO but also by NO produced by intestinal epithelial cells. The increased permeability appears to be due to the dilati
on of the tight junction, which is associated with the dephosphorylation of occuludin.
2. Effect of fatty acids on chemokine production in intestinal epithelial cells, Caco-2 cells
Butyate, short-chain fatty acid, decreased interleukin(IL)-8 production in intestinal epithelial cells.ω-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) showed no effect on IL-8 production. Oleic acid (OA) and capric acid (CA) increased IL-8 production. Proteainkinase C and phospholipase A2 were involved in signal transduction pathways for OA-induced IL-8 production but not for CA-induced IL-8 production.
3. Measurement of proteins in whole gut lavage fluid (WGLF) and feces
Either 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 were increased both in the supernatant and pellet, and the supernatant/pellet ratios of granular proteins were decreased. 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.