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.

本实验研究了蛋白酶激活受体（PAR）在人食管和胃上皮细胞上的表达及其介导细胞因子产生的机制。1. PAR-1和PAR-2在未受刺激的培养食管（HEEL）和胃（MKN-45）上皮细胞上组成型表达。此外，PAR-1和PAR-2在从人活检材料获得的食管和胃粘膜中被染色。（凝血酶）和PAR-2激动剂（胰蛋白酶和类胰蛋白酶）可诱导HEEC和MKN-45细胞产生IL-8，并呈时间和剂量依赖性。这些数据表明丝氨酸蛋白酶，如凝血酶、胰蛋白酶或类胰蛋白酶，促进培养的食管和胃上皮细胞产生IL-8，其机制与蛋白酶激活受体、G蛋白偶联受体、随后是MAPK（p-38、JNK、ERK 1/2）和转录因子（NF κ B、AP-1）的激活。这些结果表明，来自十二指肠的胰蛋白酶和来自胃肠道粘膜中肥大细胞的类胰蛋白酶可能通过PAR激活的IL-8产生而与粘膜损伤有关。

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

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

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

炎症性疾患とProtease-activated receptor(PAR)

炎症性疾病和蛋白酶激活受体（PAR）

• 发表时间: 2004
• 期刊: 医薬の門 44(1)
• 作者: Yoshida N;吉田憲正;吉田憲正
• 通讯作者: 吉田憲正