A5046332347- Cell death mechanisms and regulation
- Inflammasome and immune disorders
- interferon and immune responses
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- Gout, Hyperuricemia, Uric Acid
- Systemic Lupus Erythematosus Research
- Hematopoietic Stem Cell Transplantation
- Heme Oxygenase-1 and Carbon Monoxide
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Autoimmune and Inflammatory Disorders Research
- RNA Interference and Gene Delivery
- Hepatitis B Virus Studies
- Cytokine Signaling Pathways and Interactions
- Pancreatic function and diabetes
- Viral Infections and Vectors
- Liver physiology and pathology
- Diabetes and associated disorders
- Streptococcal Infections and Treatments
- HIV Research and Treatment
- Autophagy in Disease and Therapy
Genentech
2007-2015
Juntendo University
1997-2007
University of California, Los Angeles
2007
Molecular Oncology (United States)
2002-2005
University of Yamanashi
2003
Japan Science and Technology Agency
1998-2001
Kobe University
1999
Sapporo City General Hospital
1997-1998
Kaketsuken (Japan)
1997
Jichi Medical University
1997
Gram-negative bacteria including Escherichia coli, Citrobacter rodentium, Salmonella typhimurium, and Shigella flexneri are sensed in an ill-defined manner by intracellular inflammasome complex that activates caspase-11. We show macrophages loaded with synthetic lipid A, E. coli lipopolysaccharide (LPS), or S. typhimurium LPS activate caspase-11 independently of the receptor Toll-like 4 (TLR4). Consistent A triggering noncanonical inflammasome, containing a divergent structure antagonized...
Fas ligand (FasL) is a type II integral membrane protein homologous with tumor necrosis factor (TNF). Recent studies indicate that TNF processed to yield the soluble cytokine by metalloproteinases at cell surface of activated macrophages and T cells. In present study, we investigated whether FasL also released metalloproteinases. Treatment hydroxamic acid inhibitors matrix specifically led accumulation membrane-type (p40) on human cDNA transfectants cells, as estimated immunofluorescence...
Caspase-8 is a player in pyroptosis The activation of certain pattern-recognition receptors by pathogen-associated molecular patterns results the formation inflammasome complexes. Inflammasome complexes can initiate both maturation inflammatory cytokines and pyroptotic cell death via caspase-mediated cleavage gasdermin D (GSDMD). As now, only known regulators GSDMD macrophages are caspase-1 caspase-11. Orning et al. report an additional pathway controlling processing. YopJ, effector molecule...
Gasdermin-D (GsdmD) is a critical mediator of innate immune defense because its cleavage by the inflammatory caspases 1, 4, 5, and 11 yields an N-terminal p30 fragment that induces pyroptosis, death program important for elimination intracellular bacteria. Precisely how GsdmD triggers pyroptosis has not been established. Here we show human forms functional pores within membranes. When liberated from corresponding C-terminal p20 in presence liposomes, localized to lipid bilayer, whereas...
Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is expressed by in vitro activated natural killer (NK) cells, but the relevance of this observation to biological function NK cells has been unclear. Herein, we have demonstrated vivo induction mouse TRAIL expression on various tissue and correlated cell activation with TRAIL-mediated antimetastatic vivo. Expression was only constitutive a subset liver innate control Renca carcinoma hepatic metastases partially dependent....
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a proapoptotic member of the TNF family type II membrane proteins, which constitutes one component T cell cytotoxicity. In this study, we investigated expression and function TRAIL in human peripheral blood (PBT) cells. Although freshly isolated PBT cells did not express detectable level on their surface, remarkable was rapidly induced surface both CD4+ CD8+ upon stimulation with anti-CD3 monoclonal antibody I...
Macrophages respond to cytosolic nucleic acids by activating cysteine protease caspase-1 within a complex called the inflammasome. Subsequent cleavage and secretion of proinflammatory cytokines IL-1β IL-18 are critical for innate immunity. Here, we show that macrophages from mice lacking absent in melanoma 2 (AIM2) cannot sense double-stranded DNA fail trigger inflammasome assembly. Caspase-1 activation response intracellular pathogen Francisella tularensis also required AIM2....
Natural killer (NK) cells and interferon (IFN)-gamma have been implicated in immune surveillance against tumor development. Here we show that necrosis factor-related apoptosis-inducing ligand (TRAIL) plays a critical role the NK cell-mediated IFN-gamma-dependent surveillance. Administration of neutralizing monoclonal antibody TRAIL promoted development mice subcutaneously inoculated with chemical carcinogen methylcholanthrene (MCA). This protective effect was at least partly mediated by...
Production of type I interferon (IFN-I) is a critical host defense triggered by pattern-recognition receptors (PRRs) the innate immune system. Deubiquitinating enzyme A (DUBA), an ovarian tumor domain-containing deubiquitinating enzyme, was discovered in small interfering RNA–based screen as regulator IFN-I production. Reduction DUBA augmented PRR-induced response, whereas ectopic expression had converse effect. bound necrosis factor receptor–associated 3 (TRAF3), adaptor protein essential...
Cell death supports morphogenesis during development and homeostasis after birth by removing damaged or obsolete cells. It also curtails the spread of pathogens eliminating infected can be induced genetically programmed suicide mechanisms apoptosis, necroptosis, pyroptosis, it a consequence dysregulated metabolism, as in ferroptosis. Here, we review signaling underlying each cell-death pathway, discuss how impaired excessive activation distinct processes promote disease, highlight existing...
Pyroptosis requires the induction of gasdermin D expression by transcription factor IRF2.
The pore-forming protein gasdermin D (GSDMD) executes lytic cell death called pyroptosis to eliminate the replicative niche of intracellular pathogens. Evolution favors pathogens that circumvent this host defense mechanism. Here, we show Shigella ubiquitin ligase IpaH7.8 functions as an inhibitor GSDMD. is enteroinvasive bacterium causes hemorrhagic gastroenteritis in primates, but not rodents. contributes species specificity by ubiquitinating human, mouse, GSDMD and targeting it for...
Abstract Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ1 1 . PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting and may limit inflammation is associated with excessive cell death. Here we describe an anti-NINJ1 monoclonal antibody specifically targets mouse blocks oligomerization of NINJ1, preventing PMR....