Human and mouse granzyme A induce a proinflammatory cytokine response
Granzyme A (GzmA) is considered a major proapoptotic protease. We have discovered that GzmA-induced cell death involves rapid membrane damage that depends on the synergy between micromolar concentrations of GzmA and sublytic perforin (PFN). Ironically, GzmA and GzmB, independent of their catalytic a...
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| Hauptverfasser: | , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
October 23, 2008
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| In: |
Immunity
Year: 2008, Jahrgang: 29, Heft: 5, Pages: 720-733 |
| ISSN: | 1097-4180 |
| DOI: | 10.1016/j.immuni.2008.08.014 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://dx.doi.org/10.1016/j.immuni.2008.08.014
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| Verfasserangaben: | Sunil S. Metkar, Cheikh Menaa, Julian Pardo, Baikun Wang, Reinhard Wallich, Marina Freudenberg, Stephen Kim, Srikumar M. Raja, Lianfa Shi, Markus M. Simon, and Christopher J. Froelich |
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| 245 | 1 | 0 | |a Human and mouse granzyme A induce a proinflammatory cytokine response |c Sunil S. Metkar, Cheikh Menaa, Julian Pardo, Baikun Wang, Reinhard Wallich, Marina Freudenberg, Stephen Kim, Srikumar M. Raja, Lianfa Shi, Markus M. Simon, and Christopher J. Froelich |
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| 520 | |a Granzyme A (GzmA) is considered a major proapoptotic protease. We have discovered that GzmA-induced cell death involves rapid membrane damage that depends on the synergy between micromolar concentrations of GzmA and sublytic perforin (PFN). Ironically, GzmA and GzmB, independent of their catalytic activity, both mediated this swift necrosis. Even without PFN, lower concentrations of human GzmA stimulated monocytic cells to secrete proinflammatory cytokines (interleukin-1beta [IL-1beta], TNFalpha, and IL-6) that were blocked by a caspase-1 inhibitor. Moreover, murine GzmA and GzmA(+) cytotoxic T lymphocytes (CTLs) induce IL-1beta from primary mouse macrophages, and GzmA(-/-) mice resist lipopolysaccharide-induced toxicity. Thus, the granule secretory pathway plays an unexpected role in inflammation, with GzmA acting as an endogenous modulator. | ||
| 650 | 4 | |a Adenoviridae | |
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Cell Adhesion | |
| 650 | 4 | |a Cell Death | |
| 650 | 4 | |a Cell Line, Tumor | |
| 650 | 4 | |a Cytotoxicity, Immunologic | |
| 650 | 4 | |a Gene Knockdown Techniques | |
| 650 | 4 | |a Granzymes | |
| 650 | 4 | |a HeLa Cells | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Interleukin-1beta | |
| 650 | 4 | |a Interleukin-6 | |
| 650 | 4 | |a Jurkat Cells | |
| 650 | 4 | |a Leukocytes, Mononuclear | |
| 650 | 4 | |a Macrophages | |
| 650 | 4 | |a Mice | |
| 650 | 4 | |a Perforin | |
| 650 | 4 | |a T-Lymphocytes, Cytotoxic | |
| 650 | 4 | |a Tumor Necrosis Factor-alpha | |
| 650 | 4 | |a U937 Cells | |
| 700 | 1 | |a Menaa, Cheikh |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pardo, Julian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wang, Baikun |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wallich, Reinhard |e VerfasserIn |0 (DE-588)1059566710 |0 (DE-627)798640839 |0 (DE-576)163467781 |4 aut | |
| 700 | 1 | |a Freudenberg, Marina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kim, Stephen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Raja, Srikumar M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Shi, Lianfa |e VerfasserIn |4 aut | |
| 700 | 1 | |a Simon, Markus M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Froelich, Christopher J. |e VerfasserIn |4 aut | |
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