Toll‐like receptor 4 mediates mitochondrial DNA damage and biogenic responses after heat‐inactivatedE. coli
- 1 July 2005
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 19 (11) , 1531-1533
- https://doi.org/10.1096/fj.04-3500fje
Abstract
The body’s innate immune system closely monitors and contains bacterial products, but in pathological states the host response damages tissues by releasing inflammatory mediators that contribute to cell damage and cell death. In systemic infection by enteric bacteria, the liver’s immune role is to clear circulating microbes and their products and to produce the acute-phase response. Resident hepatic macrophages, Kuppfer cells (KC), are activated by lipopolysaccharide (LPS) and generate cytokines, especially tumor necrosis factor-α (TNF-α) and interleukins (IL), which induce reactive oxygen species (ROS) and nitric oxide (NO) production, as well as chemokines that recruit leukocytes. Elaborated factors activate receptor and nonreceptor pathways that involve mitochondria in hepatocyte necrosis and apoptosis.Mammalian cells recognize conserved microbial motifs by means of at least 10 transmembrane Toll-like receptors (TLR). TLR activation leads to immediate antimicrobial peptide and cytokine production in my...Keywords
Funding Information
- National Institutes of Health (NIH PO1 HL‐42444)
This publication has 56 references indexed in Scilit:
- Lipopolysaccharides induced increases in Fas ligand expression by Kupffer cells via mechanisms dependent on reactive oxygen speciesAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2004
- Inhibition of Interleukin-1β-induced NF-κB Activation by Calcium/Calmodulin-dependent Protein Kinase Kinase Occurs through Akt Activation Associated with Interleukin-1 Receptor-associated Kinase Phosphorylation and Uncoupling of MyD88Journal of Biological Chemistry, 2002
- The hepatocyte as a microbial product-responsive cellInnate Immunity, 2001
- Akt Stimulates the Transactivation Potential of the RelA/p65 Subunit of NF-κB through Utilization of the IκB Kinase and Activation of the Mitogen-activated Protein Kinase p38Journal of Biological Chemistry, 2001
- Cellular Events Mediated by Lipopolysaccharide-stimulated Toll-like Receptor 4Journal of Biological Chemistry, 2000
- Recent advances torwards understanding redox mechanisms in the activation of nuclear factor κbFree Radical Biology & Medicine, 2000
- Impairment of the Mitochondrial Electron Chain Transport Prevents NF-κB Activation by Hydrogen PeroxideFree Radical Biology & Medicine, 1998
- Increased Nitric Oxide Synthase Activity As A Cause of Mitochondrial Dysfunction in Rat Hepatocytes: Roles for Tumor Necrosis Factor αHepatology, 1996
- TRAF6 is a signal transducer for interleukin-1Nature, 1996
- Can hepatocytes serve as ‘activated’ immunomodulating cells in the immune response?Journal of Hepatology, 1992