INTRINSIC ANTIMICROBIAL POLYPEPTIDE IN INFLAMMATROY BOWEL DISEASE

炎症性肠病中的内在抗菌多肽

• 批准号: 11694231
• 负责人: KOHGO Yutaka
• 金额: $ 5.18万
• 依托单位: ASAHIKAWA MEDICAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11694231/
• 关键词: INTERNATIONAL SCIENCE EXCHANGE; ANTIMICROBIAL PEPTIDE; a-DEFENSIN; PANETH CELL; INFLAMMATORY BOWEL DISEASE; defensin; 自然免疫; 粘膜防御; 内因性抗菌ペプチド; paneth cell defensin; NRAMP; IL-18R; innate immunity

In this study we analyzed the expression of antimicrobial peptide in IBD intestine and colon by biological and immunological technique. We have found that 1) As well as a mouse intestine reported before, isolated crypts from normal human intestine could exocrine the antimicrobial peptide by the LPS stimulation, ex vivo. 2) In situ hybridization and RT-PCR of isolated human crypts revealed that antiomicrobial activity was caused by human a-defensin (HD-5, HD-6), released from Paneth cells. 3) Isolated human crypts from IBD intestine also produce the antimicrobial peptide as well as that of normal, noninflammed intestine. 4) Paneth cells in UC colon (metaplastic Paneth cell) also release the antimicrobial activity. 5) Metaplastic Paneth cells in human stomach also have and release antimicrobial activity that kills effectively H. Pylori.These results were submitted to publication.

本研究利用生物学和免疫学技术分析了抗菌肽在IBD肠道和结肠中的表达。我们发现：1)和以前报道的小鼠肠道一样，从正常人肠道分离的隐窝可以在体外通过内毒素刺激分泌抗菌肽。2)分离的人隐窝的原位杂交和RT-PCR结果表明，抗菌活性是由Paneth细胞释放的人α-防御素(HD-5，HD-6)引起的。3)从IBD肠道分离的人隐窝也产生抗菌肽，与正常、非炎症肠道的抗菌肽一样。4)UC结肠中的Paneth细胞(化生Paneth细胞)也释放抗菌活性。5)人胃中的化生潘氏细胞也具有并释放有效杀死幽门螺杆菌的抗菌活性。这些结果已提交发表。

项目成果

Ohtake T.: "Proline-rich antimicrobial peptide, PR-39 gene transduction altered invasive activity and actin structure in human hepatocellular carcinoma cells"Br J Cancer.. 81. 393-403 (1999)

Ohtake T.：“富含脯氨酸的抗菌肽、PR-39 基因转导改变了人肝细胞癌细胞的侵袭活性和肌动蛋白结构”Br J Cancer.. 81. 393-403 (1999)

T Ayabe, A Maemoto T Ashida, F Orii, Jiro Watari Y kkohgo: "Functional studies colonic Paneth cells in patients with ulcerative colitis"Gastroenterology. 120 5 suppl. 2668 (2001)

T Ayabe、A Maemoto T Ashida、F Orii、Jiro Watari Y kkohgo：“溃疡性结肠炎患者结肠潘氏细胞的功能研究”胃肠病学。

K Tanaka Y Fujimoto, M Suzuki, Y Suzuki, T Ohtake, H Saito, Y Kohgo: "P13-kinase p85a is a target molecule of proline-rich antimicrobial peptide to suppress proliferation of ras-transformed cells"Jpn J. Cancer Res. 92. 959-967 (2001)

K Tanaka Y Fujimoto、M Suzuki、Y Suzuki、T Ohtake、H Saito、Y Kohgo：“P13 激酶 p85a 是富含脯氨酸的抗菌肽的靶分子，可抑制 ras 转化细胞的增殖”Jpn J. Cancer Res。

Honda M, et al.: "Expression of glucocoiticoid receptor βin lymphocytes of patients with glucocorticord-resistant ulcerative colitis."Gastroenterology. 118. 859-866 (2000)

Honda M 等人：“糖皮质激素耐药性溃疡性结肠炎患者淋巴细胞中的糖皮质激素受体 β 表达。胃肠病学”118. 859-866 (2000)。

K Tanaka, Y Fujimoto, M Suzuki, Y Suzuki, T Ohtake, H Saito, Y Kohgo: "P13-kinase p85a is a target molecule of proline-rich antimicrobial peptide to suppress proliferation of ras-transformed cells"Jpn J. Cancer Res. 92. 959-967 (2001)

K Tanaka、Y Fujimoto、M Suzuki、Y Suzuki、T Ohtake、H Saito、Y Kohgo：“P13 激酶 p85a 是富含脯氨酸的抗菌肽的靶分子，可抑制 ras 转化细胞的增殖”Jpn J. Cancer Res