Studies on recognition mechanism of oral microbes-derived lipopeptides by Toll-like receptors

Toll样受体识别口腔微生物脂肽机制的研究

• 批准号: 15390549
• 负责人: SHIBATA Ken-ichiro
• 金额: $ 8.32万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-15390549/
• 关键词: Toll-like receptor 2; lipopeptides; lipopeoteins; Leucine-rich repeats; apoptosis; Toll-like receptor; ペプチドグリカン; Toll様受容体

Toll-like receptor 2 (TLR2)plays a key role in the recognition of microbial lipoproteins/lipoeppetides. However, details in molecular mechanisms of the recognition still remains unknown. This study was therefore carried out to determine the molecular mechanism by which TLR2 recognizes microbial lipoproteins/lipoeppetides.We have found the following findings.1.The level of the activity of bacterial triacylated lipopeptides to stimulate macrophages was lower than that of mycoplasmal diacylated lipoepptides.2.Both lipid and peptide portions of mycoplasmal diacylated lipopeptides are involved in the recognition by TLR2.3.Leucine residues at positions 107,112 and 115 are involved in the recognition of mycoplasmal lipoproteins/lipopeptide and S.aureus peptidoglycans by TLR2 in combination with TLR6.4.There is at least one leucine residue in all 8 leucine-rich repeats of TLR2 which is responsible for the the recognition of mycoplasmal lipoproteins/lipopeptide and S.aureus peptidoglycans by TLR2 in combination with TLR6.5.Leucine residues in β-sheet structure of leucine-rich repeats are involved in the recognition of mycoplasmal lipopeptides by TLR2 in combination with TLR6.6.Mycoplasmal lipoproteins possesses the activity to induce apoptosis of HEK293 cells through TLR2/TLR2 and the activity is mediated by FADD and MyD88 downstream of TLR2.

Toll样受体2（TLR 2）在微生物脂蛋白/脂肽的识别中起关键作用。然而，识别的分子机制的细节仍然未知。因此，进行本研究以确定TLR 2识别微生物脂蛋白的分子机制。结果表明：1.细菌三酰化脂肽对巨噬细胞的刺激活性低于支原体二酰化脂肽; 2.支原体二酰化脂肽的脂质和肽段均参与TLR 2的识别; 3. 107,112和115参与TLR 2与TLR6.4联合识别支原体脂蛋白/脂肽和金黄色葡萄球菌肽聚糖。TLR 2的所有8个富含亮氨酸的重复序列中至少有一个亮氨酸残基负责TLR 2与TLR6.5联合识别支原体脂蛋白/脂肽和金黄色葡萄球菌肽聚糖。TLR 2和TLR6.6共同作用于支原体脂肽，支原体脂蛋白具有通过TLR 2/TLR 2诱导HEK 293细胞凋亡的活性，该活性由TLR 2下游的FADD和MyD 88介导。

项目成果

Possible roles of Toll-like receptor 2/6 and extracellular ATP in mycoplasmal lipoprpotein-induced cell activation and death

Toll样受体2/6和细胞外ATP在支原体脂蛋白诱导的细胞活化和死亡中的可能作用

• 发表时间: 2004
• 期刊: Journal of Oral Bioscience 46・4
• 作者: T.Into;K.Shibata
• 通讯作者: K.Shibata

Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal disease

• DOI: 10.1128/iai.72.3.1318-1325.2004
• 发表时间: 2004-03-01
• 期刊: INFECTION AND IMMUNITY
• 影响因子: 3.1
• 作者: Hasebe, A;Yoshimura, A;Shibata, K
• 通讯作者: Shibata, K

Involvement of leucine residues at positions 107, 112, and 115 in a leucine-rich repeat motif of human toll-like receptor 2 in the recognition of diacylated lipoproteins and lipopeptides and Staphylococcus aureus peptidoglycans

• DOI: 10.4049/jimmunol.171.7.3675
• 发表时间: 2003-10-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Fujita, M;Into, T;Shibata, K
• 通讯作者: Shibata, K

Stimulation of human Toll-like receptor(TLR) 2 and TLR6 with membrane lipoproteins of Mycoplasma fermentans induces apoptotic cell death after NF-kappaB activation

发酵支原体膜脂蛋白刺激人 Toll 样受体 (TLR) 2 和 TLR6 诱导 NF-kappaB 激活后细胞凋亡

• 发表时间: 2004
• 期刊: Cellular Microbiology 6(2)
• 作者: T.Into;K.Kiura;M.Yasuda;H.Kataoka;N.Inoue;A.Hasebe;K.Takeda;S.Akira;K.Shibata
• 通讯作者: K.Shibata

Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by toll-like receptors 2 and 6

• DOI: 10.1128/iai.72.3.1657-1665.2004
• 发表时间: 2004-03-01
• 期刊: INFECTION AND IMMUNITY
• 影响因子: 3.1
• 作者: Okusawa, T;Fujita, M;Shibata, KI
• 通讯作者: Shibata, KI