高迁移率族蛋白B1(high mobility group box 1protein,HMGB1)是一种非组蛋白染色质结合蛋白,参与DNA修复、重组和基因转录,当细胞损伤时释放到胞外,成为重要的晚期炎症因子参与信号转导。近年的研究表明,HMGB1释放到胞外发挥着广泛的生...高迁移率族蛋白B1(high mobility group box 1protein,HMGB1)是一种非组蛋白染色质结合蛋白,参与DNA修复、重组和基因转录,当细胞损伤时释放到胞外,成为重要的晚期炎症因子参与信号转导。近年的研究表明,HMGB1释放到胞外发挥着广泛的生物学效应,并在很多疾病中起着促进炎症的作用,提示HMGB1有可能成为治疗这些疾病的靶标。本文介绍了HMGB1发挥致炎活性的过程,并指出抑制HMGB1致炎活性的相关策略,并阐述与这些策略有关的中药单体的研究进展。展开更多
The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, i...The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, insects and parasitic nematodes, but is completely absent in mammals. Exposure to antigens containing chitin- or chitin-like structures sometimes induces strong T helper type-I responses in mammals, which may be associated with the induction of mammalian chitinases. Chitinase 3-like-1 (CHI3L1), a member of the mammalian chitinase family, is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease, hepatitis and asthma. In addition, CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma, colon cancer, breast cancer and malignant melanoma. Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown, CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix. CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways. Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3Ll-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.展开更多
文摘高迁移率族蛋白B1(high mobility group box 1protein,HMGB1)是一种非组蛋白染色质结合蛋白,参与DNA修复、重组和基因转录,当细胞损伤时释放到胞外,成为重要的晚期炎症因子参与信号转导。近年的研究表明,HMGB1释放到胞外发挥着广泛的生物学效应,并在很多疾病中起着促进炎症的作用,提示HMGB1有可能成为治疗这些疾病的靶标。本文介绍了HMGB1发挥致炎活性的过程,并指出抑制HMGB1致炎活性的相关策略,并阐述与这些策略有关的中药单体的研究进展。
基金Supported by NIH (DK64289,DK74454,DK43351 and DK80070)grants from the Eli and Edythe L.Broad Medical FoundationAmerican Gastroenterological Association Foundation for Digestive Health and Nutrition to Mizoguchi E
文摘The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, insects and parasitic nematodes, but is completely absent in mammals. Exposure to antigens containing chitin- or chitin-like structures sometimes induces strong T helper type-I responses in mammals, which may be associated with the induction of mammalian chitinases. Chitinase 3-like-1 (CHI3L1), a member of the mammalian chitinase family, is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease, hepatitis and asthma. In addition, CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma, colon cancer, breast cancer and malignant melanoma. Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown, CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix. CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways. Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3Ll-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.