The TLR4/TRIF-Mediated Activation of NLRP3 Inflammasome Underlies Endotoxin-Induced Liver Injury in Mice
Administration of heat-killed Propionibacterium acnes renders mice highly susceptible to LPS. After LPS challenge P. acnes-primed mice promptly show hypothermia, hypercoagulation (disseminated intravascular coagulation), elevation of serum proinflammatory cytokine levels, and high mortality. The s...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2010-01-01
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| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2010/641865 |
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| Summary: | Administration of heat-killed Propionibacterium acnes renders mice highly susceptible to LPS. After LPS challenge P. acnes-primed mice promptly show hypothermia, hypercoagulation (disseminated intravascular coagulation), elevation of serum proinflammatory cytokine levels, and high mortality. The surviving mice develop liver injury. As previously reported, IL-18 plays a pivotal role in the development of this liver injury. Many cell types including macrophages constitutively store IL-18 as biologically inactive precursor (pro) form. Upon appropriate stimulation exemplified by TLR4 engagement, the cells secrete biologically active IL-18 by cleaving pro-IL-18 with caspase-1. Caspase-1 is also constitutively produced as a zymogen in macrophages. Recently, NLRP3, a cytoplasmic pathogen sensor, has been demonstrated to be involved in the activation of caspase-1. Here, we review the molecular mechanisms for the liver injuries, particularly focusing on the TLR4/NLRP3-mediated caspase-1 activation process, with a brief introduction of the mechanism underlying P. acnes-induced sensitization to LPS. |
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| ISSN: | 1687-6121 1687-630X |