例如:"lncRNA", "apoptosis", "WRKY"

A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death.

Elife. 2018 Dec 07;7
Shigetoshi Yokoyama 1 , Yan Cai 1 , Miyuki Murata 1 , Takeshi Tomita 1 , Mitsuhiro Yoneda 1 , Lei Xu 1 , Aprile L Pilon 2 , Raul E Cachau 3 , Shioko Kimura 1
Shigetoshi Yokoyama 1 , Yan Cai 1 , Miyuki Murata 1 , Takeshi Tomita 1 , Mitsuhiro Yoneda 1 , Lei Xu 1 , Aprile L Pilon 2 , Raul E Cachau 3 , Shioko Kimura 1
+ et al

[No authors listed]

Author information
  • 1 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, United States.
  • 2 APCBIo Innovations Inc., Rockville, United States.
  • 3 Advanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Leidos Biomedical Inc., Frederick, United States.

摘要


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.

KEYWORDS: LPS, cancer cell death, immunology, inflammation, mouse, non-canonical infammasome pathway, pyroptosis, secretoglobin3A2, syndecan-1