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

被引：59

作者：

Yokoyama, Shigetoshi ^{[1
]}

Cai, Yan ^{[1
]}

Murata, Miyuki ^{[1
]}

Tomita, Takeshi ^{[1
]}

Yoneda, Mitsuhiro ^{[1
]}

Xu, Lei ^{[1
]}

Pilon, Aprile L. ^{[2
]}

Cachau, Raul E. ^{[3
]}

Kimura, Shioko ^{[1
]}

机构：

[1] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA

[2] APCBIo Innovat Inc, Rockville, MD USA

[3] Leidos Biomed Inc, Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD USA

来源：

ELIFE | 2018年 / 7卷

关键词：

NONCANONICAL INFLAMMASOME ACTIVATION; ALLERGIC AIRWAY INFLAMMATION; SECRETOGLOBIN; 3A2; GROWTH-FACTOR; EXPRESSION; PROTEIN; SUPERFAMILY; UTEROGLOBIN; MECHANISM; ADHESION;

D O I：

10.7554/eLife.37854

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页数：25

共 49 条

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