Cathepsins are required for Toll-like receptor 9 responses
| Autor: | Fumi Matsumoto, Toshihiko Kobayashi, Ryutaroh Fukui, Natsuko Tanimura, Sachiko Akashi-Takamura, Shin-ichiroh Saitoh, Kensuke Miyake, Yutaka Kusumoto, Kazunori Konno |
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| Rok vydání: | 2008 |
| Předmět: |
DNA
Bacterial Biophysics chemical and pharmacologic phenomena Cathepsin E Cathepsin F Biology Ligands Biochemistry Cathepsin A Cathepsin B Cell Line Cathepsin C Mice Cathepsin O immune system diseases Cathepsin H parasitic diseases Animals Humans RNA Messenger Enzyme Inhibitors Molecular Biology Cathepsin B-Lymphocytes Macrophages Gene Transfer Techniques NF-kappa B hemic and immune systems Cell Biology Cathepsins Molecular biology Immunity Innate Cell biology Oligodeoxyribonucleotides Toll-Like Receptor 9 Mutagenesis Site-Directed CpG Islands Spleen |
| Zdroj: | Biochemical and Biophysical Research Communications. 367:693-699 |
| ISSN: | 0006-291X |
| Popis: | Toll-like receptors (TLR) recognize a variety of microbial products and activate defense responses. Pathogen sensing by TLR2/4 requires accessory molecules, whereas little is known about a molecule required for DNA recognition by TLR9. After endocytosis of microbes, microbial DNA is exposed and recognized by TLR9 in lysosomes. We here show that cathepsins, lysosomal cysteine proteases, are required for TLR9 responses. A cell line Ba/F3 was found to be defective in TLR9 responses despite enforced TLR9 expression. Functional cloning with Ba/F3 identified cathepsin B/L as a molecule required for TLR9 responses. The protease activity was essential for the complementing effect. TLR9 responses were also conferred by cathepsin S or F, but not by cathepsin H. TLR9-dependent B cell proliferation and CD86 upregulation were apparently downregulated by cathepsin B/L inhibitors. Cathepsin B inhibitor downregulated interaction of CpG-B with TLR9 in 293T cells. These results suggest roles for cathepsins in DNA recognition by TLR9. |
| Databáze: | OpenAIRE |
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