<it>Legionella pneumophila </it>induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages
<p>Abstract</p> <p>Background</p> <p><it>Legionella pneumophila </it>(LPN) can cause a lethal infectious disease with a marked inflammatory response in humans. However, the mechanism of this severe inflammation remains poorly understood. Since necrosis is kn...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-11-01
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| Series: | Respiratory Research |
| Online Access: | http://respiratory-research.com/content/11/1/158 |
| _version_ | 1818956640877019136 |
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| author | Kakeya Hiroshi Izumikawa Koichi Seki Masafumi Hasegawa Hiroo Nakamura Shigeki Yanagihara Katsunori Morinaga Yoshitomo Yamamoto Yoshihiro Yamada Yasuaki Kohno Shigeru Kamihira Shimeru |
| author_facet | Kakeya Hiroshi Izumikawa Koichi Seki Masafumi Hasegawa Hiroo Nakamura Shigeki Yanagihara Katsunori Morinaga Yoshitomo Yamamoto Yoshihiro Yamada Yasuaki Kohno Shigeru Kamihira Shimeru |
| author_sort | Kakeya Hiroshi |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p><it>Legionella pneumophila </it>(LPN) can cause a lethal infectious disease with a marked inflammatory response in humans. However, the mechanism of this severe inflammation remains poorly understood. Since necrosis is known to induce inflammation, we investigated whether LPN induces necrosis in macrophages. We also analyzed the involvement of lysosomal cathepsin B in LPN-induced cell death.</p> <p>Methods</p> <p>The human monocytic cell line THP-1 was infected with LPN, NUL1 strain. MG132-treated cells were used as apoptotic control cells. After infection, the type of cell death was analyzed by using microscopy, LDH release and flow cytometry. As a proinflammatory mediator, high-mobility group box 1 (HMGB-1), was measured. Cathepsin B activity was also measured and the inhibitory effects of cathepsin B on LPN-induced cell death were analyzed.</p> <p>Results</p> <p>THP-1 cells after treatment with high dose of LPN showed necrotic features with releasing HMGB-1. This necrosis and the HMGB-1 release were inhibited by a specific lysosomal cathepsin B inhibitor and were characterized by a rapid and high activation of cathepsin B that was not observed in apoptotic control cells. The necrosis was also accompanied by cathepsin B-dependent poly(ADP-ribose) polymerase (PARP) cleavage.</p> <p>Conclusions</p> <p>We demonstrate here that <it>L. pneumophila </it>rapidly induces cathepsin B-dependent necrosis in a dose-dependent manner and releases a proinflammatory mediator, HMGB-1, from macrophages. This report describes a novel aspect of the pathogenesis of Legionnaires' disease and provides a possible therapeutic target for the regulation of inflammation.</p> |
| first_indexed | 2024-12-20T10:57:11Z |
| format | Article |
| id | doaj.art-787329397a7a46b1869813ef3622a9e5 |
| institution | Directory Open Access Journal |
| issn | 1465-9921 |
| language | English |
| last_indexed | 2024-12-20T10:57:11Z |
| publishDate | 2010-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-787329397a7a46b1869813ef3622a9e52022-12-21T19:43:07ZengBMCRespiratory Research1465-99212010-11-0111115810.1186/1465-9921-11-158<it>Legionella pneumophila </it>induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophagesKakeya HiroshiIzumikawa KoichiSeki MasafumiHasegawa HirooNakamura ShigekiYanagihara KatsunoriMorinaga YoshitomoYamamoto YoshihiroYamada YasuakiKohno ShigeruKamihira Shimeru<p>Abstract</p> <p>Background</p> <p><it>Legionella pneumophila </it>(LPN) can cause a lethal infectious disease with a marked inflammatory response in humans. However, the mechanism of this severe inflammation remains poorly understood. Since necrosis is known to induce inflammation, we investigated whether LPN induces necrosis in macrophages. We also analyzed the involvement of lysosomal cathepsin B in LPN-induced cell death.</p> <p>Methods</p> <p>The human monocytic cell line THP-1 was infected with LPN, NUL1 strain. MG132-treated cells were used as apoptotic control cells. After infection, the type of cell death was analyzed by using microscopy, LDH release and flow cytometry. As a proinflammatory mediator, high-mobility group box 1 (HMGB-1), was measured. Cathepsin B activity was also measured and the inhibitory effects of cathepsin B on LPN-induced cell death were analyzed.</p> <p>Results</p> <p>THP-1 cells after treatment with high dose of LPN showed necrotic features with releasing HMGB-1. This necrosis and the HMGB-1 release were inhibited by a specific lysosomal cathepsin B inhibitor and were characterized by a rapid and high activation of cathepsin B that was not observed in apoptotic control cells. The necrosis was also accompanied by cathepsin B-dependent poly(ADP-ribose) polymerase (PARP) cleavage.</p> <p>Conclusions</p> <p>We demonstrate here that <it>L. pneumophila </it>rapidly induces cathepsin B-dependent necrosis in a dose-dependent manner and releases a proinflammatory mediator, HMGB-1, from macrophages. This report describes a novel aspect of the pathogenesis of Legionnaires' disease and provides a possible therapeutic target for the regulation of inflammation.</p>http://respiratory-research.com/content/11/1/158 |
| spellingShingle | Kakeya Hiroshi Izumikawa Koichi Seki Masafumi Hasegawa Hiroo Nakamura Shigeki Yanagihara Katsunori Morinaga Yoshitomo Yamamoto Yoshihiro Yamada Yasuaki Kohno Shigeru Kamihira Shimeru <it>Legionella pneumophila </it>induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages Respiratory Research |
| title | <it>Legionella pneumophila </it>induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages |
| title_full | <it>Legionella pneumophila </it>induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages |
| title_fullStr | <it>Legionella pneumophila </it>induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages |
| title_full_unstemmed | <it>Legionella pneumophila </it>induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages |
| title_short | <it>Legionella pneumophila </it>induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages |
| title_sort | it legionella pneumophila it induces cathepsin b dependent necrotic cell death with releasing high mobility group box1 in macrophages |
| url | http://respiratory-research.com/content/11/1/158 |
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