title: The TLR4/TRIF-Mediated Activation of NLRP3 Inflammasome Underlies Endotoxin-Induced Liver Injury in Mice.
abstract: 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.
authors.affiliation: Department of Microbiology, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya 663-8501, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Michiko
authors.initials: M
authors.lastname: Imamura
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakanishi