A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death
Intracellular lipopolysaccharide (LPS) triggers the non-canonical inflammasome pathway, resulting in pyroptosis of innate immune cells. In addition to its well-known proinflammatory role, LPS can directly cause regression of some tumors, although the underlying mechanism has remained unknown. Here w...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2018-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/37854 |
| _version_ | 1811253015382851584 |
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| author | Shigetoshi Yokoyama Yan Cai Miyuki Murata Takeshi Tomita Mitsuhiro Yoneda Lei Xu Aprile L Pilon Raul E Cachau Shioko Kimura |
| author_facet | Shigetoshi Yokoyama Yan Cai Miyuki Murata Takeshi Tomita Mitsuhiro Yoneda Lei Xu Aprile L Pilon Raul E Cachau Shioko Kimura |
| author_sort | Shigetoshi Yokoyama |
| collection | DOAJ |
| description | Intracellular lipopolysaccharide (LPS) triggers the non-canonical inflammasome pathway, resulting in pyroptosis of innate immune cells. In addition to its well-known proinflammatory role, LPS can directly cause regression of some tumors, although the underlying mechanism has remained unknown. Here we show that secretoglobin(SCGB)3A2, a small protein predominantly secreted in airways, chaperones LPS to the cytosol through the cell surface receptor syndecan-1; this leads to pyroptotic cell death driven by caspase-11. SCGB3A2 and LPS co-treatment significantly induced pyroptosis of macrophage RAW264.7 cells and decreased cancer cell proliferation in vitro, while SCGB3A2 treatment resulted in reduced progression of xenograft tumors in mice. These data suggest a conserved function for SCGB3A2 in the innate immune system and cancer cells. These findings demonstrate a critical role for SCGB3A2 as an LPS delivery vehicle; they reveal one mechanism whereby LPS enters innate immune cells leading to pyroptosis, and they clarify the direct effect of LPS on cancer cells. |
| first_indexed | 2024-04-12T16:44:17Z |
| format | Article |
| id | doaj.art-70789844fe5a470fb8b5e29c4c3f6091 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:44:17Z |
| publishDate | 2018-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-70789844fe5a470fb8b5e29c4c3f60912022-12-22T03:24:39ZengeLife Sciences Publications LtdeLife2050-084X2018-12-01710.7554/eLife.37854A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell deathShigetoshi Yokoyama0https://orcid.org/0000-0003-4175-0548Yan Cai1Miyuki Murata2Takeshi Tomita3Mitsuhiro Yoneda4Lei Xu5Aprile L Pilon6Raul E Cachau7Shioko Kimura8https://orcid.org/0000-0001-9627-6818Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, United StatesAPCBIo Innovations Inc., Rockville, United StatesAdvanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Leidos Biomedical Inc., Frederick, United StatesLaboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, United StatesIntracellular lipopolysaccharide (LPS) triggers the non-canonical inflammasome pathway, resulting in pyroptosis of innate immune cells. In addition to its well-known proinflammatory role, LPS can directly cause regression of some tumors, although the underlying mechanism has remained unknown. Here we show that secretoglobin(SCGB)3A2, a small protein predominantly secreted in airways, chaperones LPS to the cytosol through the cell surface receptor syndecan-1; this leads to pyroptotic cell death driven by caspase-11. SCGB3A2 and LPS co-treatment significantly induced pyroptosis of macrophage RAW264.7 cells and decreased cancer cell proliferation in vitro, while SCGB3A2 treatment resulted in reduced progression of xenograft tumors in mice. These data suggest a conserved function for SCGB3A2 in the innate immune system and cancer cells. These findings demonstrate a critical role for SCGB3A2 as an LPS delivery vehicle; they reveal one mechanism whereby LPS enters innate immune cells leading to pyroptosis, and they clarify the direct effect of LPS on cancer cells.https://elifesciences.org/articles/37854secretoglobin3A2LPSsyndecan-1pyroptosisnon-canonical infammasome pathwaycancer cell death |
| spellingShingle | Shigetoshi Yokoyama Yan Cai Miyuki Murata Takeshi Tomita Mitsuhiro Yoneda Lei Xu Aprile L Pilon Raul E Cachau Shioko Kimura A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death eLife secretoglobin3A2 LPS syndecan-1 pyroptosis non-canonical infammasome pathway cancer cell death |
| title | A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death |
| title_full | A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death |
| title_fullStr | A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death |
| title_full_unstemmed | A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death |
| title_short | A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death |
| title_sort | novel pathway of lps uptake through syndecan 1 leading to pyroptotic cell death |
| topic | secretoglobin3A2 LPS syndecan-1 pyroptosis non-canonical infammasome pathway cancer cell death |
| url | https://elifesciences.org/articles/37854 |
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