Intradermal transfer of caspase-1 (CASP1) DNA into mouse dissects: role of CASP1 in interleukin-1β associated skin inflammation and apoptotic cell death

1999 ◽  
Vol 21 (1) ◽  
pp. 49-58 ◽  
Author(s):  
Kunihiko Asahi ◽  
Hitoshi Mizutani ◽  
Minoru Tanaka ◽  
Masayuki Miura ◽  
Kei-ichi Yamanaka ◽  
...  
2015 ◽  
Vol 84 (1) ◽  
pp. 172-186 ◽  
Author(s):  
Moo-Seung Lee ◽  
Haenaem Kwon ◽  
Eun-Young Lee ◽  
Dong-Jae Kim ◽  
Jong-Hwan Park ◽  
...  

Shiga toxin (Stx)-mediated immune responses, including the production of the proinflammatory cytokines tumor necrosis-α (TNF-α) and interleukin-1β (IL-1β), may exacerbate vascular damage and accelerate lethality. However, the immune signaling pathway activated in response to Stx is not well understood. Here, we demonstrate that enzymatically active Stx, which leads to ribotoxic stress, triggers NLRP3 inflammasome-dependent caspase-1 activation and IL-1β secretion in differentiated macrophage-like THP-1 (D-THP-1) cells. The treatment of cells with a chemical inhibitor of glycosphingolipid biosynthesis, which suppresses the expression of the Stx receptor globotriaosylceramide and subsequent endocytosis of the toxin, substantially blocked activation of the NLRP3 inflammasome and processing of caspase-1 and IL-1β. Processing and release of both caspase-1 and IL-1β were significantly reduced or abolished in Stx-intoxicated D-THP-1 cells in which the expression of NLRP3 or ASC was stably knocked down. Furthermore, Stx mediated the activation of caspases involved in apoptosis in an NLRP3- or ASC-dependent manner. In Stx-intoxicated cells, the NLRP3 inflammasome triggered the activation of caspase-8/3, leading to the initiation of apoptosis, in addition to caspase-1-dependent pyroptotic cell death. Taken together, these results suggest that Stxs trigger the NLRP3 inflammasome pathway to release proinflammatory IL-1β as well as to promote apoptotic cell death.


2003 ◽  
Vol 35 (9) ◽  
pp. 585-592 ◽  
Author(s):  
Richard S. Hotchkiss ◽  
Kevin W. Tinsley ◽  
Irene E. Karl

2001 ◽  
Vol 170 (2) ◽  
pp. 132-140 ◽  
Author(s):  
R. McLaughlin ◽  
C. J. Kelly ◽  
E. Kay ◽  
D. Bouchier-Hayes

2009 ◽  
Vol 101 (4) ◽  
pp. 628-636 ◽  
Author(s):  
B Pauwels ◽  
J B Vermorken ◽  
A Wouters ◽  
J Ides ◽  
S Van Laere ◽  
...  

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