Role of protease-activated receptor in mucosal injury of upper alimentary tract

蛋白酶激活受体在上消化道黏膜损伤中的作用

• 批准号: 15590672
• 负责人: YOSHIDA Norimasa
• 金额: $ 1.6万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590672/
• 关键词: protease-activated receptor(PAR); esophagus; stomach; thrombin; trypsin; tryptase; IL-8; NFkappaB; PAR (protease-activated receptor); サイトカイン; アスピリン; protease-activated receptor(PAR); 食道上皮細胞; 逆流性食道炎; 胃食道逆流症; interleukin-8(IL-8); NfkappaB

I investigated expression of protease-activated receptor(PAR) on both human esophageal and gastric epithelial cells, and mechanisms of PAR-mediated cytokine production from these cultured cells.1.PAR-1 and PAR-2 were constitutively expressed on unstimulated cultured esophageal (HEEL) and gastric (MKN-45) epithelial cells. In addition, PAR-1 and PAR-2 were stained in the esophageal and gastric mucosa obtained from human biopsy materials.2.PAR-1 agonist (thrombin) and PAR-2 agonist (trypsin and tryptase) resulted in induction of IL-8 production from HEEC and MKN-45 cells time- and dose- dependently.3.Increased IL-8 production was significantly by antibody to PAR, MAPK inhibitor and transfection of NFkappaB or AP-1 mutant vector.These data indicate that serine proteases, such as thrombin, trypsin or tryptase, promote IL-8 production from cultured esophageal and gastric epithelial cells, which mechanisms are associated with activation of protease-activated receptor, G-protein coupled receptor, followed by the activation of MAPK(p-38, JNK, ERK1/2) and transcription factor (NFkappaB, AP-1). These results suggest that trypsin which comes in esophagus and stomach from duodenum and tryptase derived from mast cells in the gastrointestinal mucosa may be related to mucosal injury via PAR-activated IL-8 production.

我研究了蛋白酶激活受体（PAR）在人类食管和胃皮细胞上均在这些培养细胞中的PAR介导的细胞因子产生的机制。1.PAR-1和PAR-2在未刺激的培养的食道（脚跟）和胃（MKN-45）上皮细胞。此外，将PAR-1和PAR-2染色在从人体活检材料中获得的食道和胃粘膜中染色。2.Par-1激动剂（凝血酶）和PAR-2激动剂（胰蛋白酶和胰蛋白酶）导致IL-8诱导HEEC和MKN-45细胞的产生时间和剂量依赖性。3。IL-8产生的抗体对PAR，MAPK抑制剂以及NFKAPPAB或AP-1突变体载体的转染显着。作为凝血酶，胰蛋白酶或胰蛋白酶，促进培养的食管和胃皮细胞产生的IL-8产生，这些机制与蛋白酶激活受体激活G蛋白偶联受体有关，然后激活MAPK（P-38，JNK，JNK，JNK，JNK ，ERK1/2）和转录因子（NFKAPPAB，AP-1）。这些结果表明，胃肠道粘膜中的肥大细胞衍生出的可食管和胃的胰蛋白酶可能通过PAR激活的IL-8产生与粘膜损伤有关。

项目成果

PAR2を介した食道上皮細胞からのIL-8産生と食道粘膜の炎症

食管上皮细胞产生IL-8和PAR2介导的食管粘膜炎症

• 发表时间: 2004
• 期刊: 日薬理誌 124
• 作者: Yoshida N;吉田憲正
• 通讯作者: 吉田憲正

Interleukin-8 expression in the esophageal mucosa of patients with gastroesophageal reflux disease

胃食管反流病患者食管黏膜白细胞介素8的表达

• 发表时间: 2003
• 期刊: Scand J Gastoenterol 39
• 作者: Yoshida N;吉田憲正;吉田憲正;霜澤 真;Yoshida N.;Yoshida N.;吉田憲正;Yoshida N
• 通讯作者: Yoshida N

食道粘膜防御機構の破綻と食道粘膜の炎症

食管粘膜防御机制的破坏与食管粘膜炎症

• 发表时间: 2003
• 期刊: 診断と治療 91(1)
• 作者: Yoshida N;吉田憲正;吉田憲正;霜澤 真;Yoshida N.;Yoshida N.;吉田憲正;Yoshida N;吉田憲正
• 通讯作者: 吉田憲正

Trypsin activates human esophageal epithelial cells to produce inflammatory cytokines through protease-activate receptor 2.

胰蛋白酶通过蛋白酶激活受体2激活人食管上皮细胞产生炎症细胞因子。

• 发表时间: 2004
• 期刊: Gastroenterol 126(4)
• 作者: Yoshida N

炎症と接着分子

炎症和粘附分子

• 发表时间: 2004
• 期刊: プロテアーゼインヒビター 基礎編
• 作者: Yoshida N;吉田憲正;吉田憲正;霜澤 真
• 通讯作者: 霜澤 真