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.

在这项研究中，我们通过生物学和免疫学技术分析了IBD肠和结肠中抗菌肽的表达。我们发现1）以及以前报道的小鼠肠道，从正常人肠中分离的隐窝可以通过LPS刺激离体外分泌抗菌肽。 2）原位杂交和分离的人隐窝的RT-PCR表明，抗生素活性是由人类A-防御素（HD-5，HD-6）从Paneth细胞中释放出来的。 3）从IBD肠中分离的人隐窝还会产生抗菌肽以及正常的非炎症肠。 4）UC结肠中的Paneth细胞（Explastic Paneth细胞）也释放了抗菌活性。 5）人类胃中的化生层细胞还具有并释放有效杀死幽门螺杆菌的抗菌活性。这些结果已提交出版。

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)。

Fujimoto Y.: "Alteration of genomic structure and/or expression of cancer associated qenes in hepatocellular carcinomal"Rinsho Byori.. 46. 9-14 (1998)

Fujimoto Y.：“肝细胞癌中基因组结构和/或癌症相关基因表达的改变”Rinsho Byori.. 46. 9-14 (1998)