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A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death
- Source :
- eLife, Vol 7 (2018)
- Publication Year :
- 2018
- Publisher :
- eLife Sciences Publications Ltd, 2018.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 7
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.70789844fe5a470fb8b5e29c4c3f6091
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.37854