Toll-like receptors (TLRs) can orchestrate an inflammatory response upon activation by pathogen-associated motifs and release of endogenous stress ligands during tissue injury. The kidney constitutively expresses most TLRs, including TLR4. The function of TLR4 during the inflammation, tubular atrophy, and fibrosis that accompany progressive renal injury is unknown. Here, we subjected wild-type ...

PURPOSE To investigate the importance of Toll-like receptor 4 (TLR4) expression on hepatocytes obtained from Chronic Hepatitis B patients as well as on hepatocellular carcinoma HepG2 and HepG2.2.15 cell lines. METHODS Expression of TLR4 in liver tissues was determined by immunohistochemistry in 75 patients with CHB and in10 healthy controls. The protein and mRNA 1eve1s of TLR4 in hepatocellul...

Lipopolysaccharide (LPS), also known as endotoxin, activates the innate immune response through toll-like receptor 4 (TLR4) and its coreceptor, MD-2. MD-2 has a unique hydrophobic cavity that directly binds to lipid A, the active center of LPS. Tetraacylated lipid IVa, a synthetic lipid A precursor, acts as a weak agonist to mouse TLR4/MD-2, but as an antagonist to human TLR4/MD-2. However, it ...

Acute lung injury (ALI) is a severe complication of orthotopic liver transplantation (OLT) with unclear underline mechanism. Toll-like receptor 4 (TLR4) has been identified as a key receptor mediating inflammation. We hypothesized that TLR4-mediated pulmonary inflammation may contribute to development of ALI during OLT. Patients with or without ALI were observed for serum cytokines and expressi...

Ischemia/reperfusion injury (IRI) may activate innate immunity through the engagement of TLRs by endogenous ligands. TLR4 expressed within the kidney is a potential mediator of innate activation and inflammation. Using a mouse model of kidney IRI, we demonstrated a significant increase in TLR4 expression by tubular epithelial cells (TECs) and infiltrating leukocytes within the kidney following ...

Gangliosides participate in various cellular events of the central nervous system and have been closely implicated in many neuronal diseases. However, the precise molecular mechanisms underlying the pathological activity of gangliosides are poorly understood. Here we report that toll-like receptor 4 (TLR4) may mediate the ganglioside-triggered inflammation in glia, brain resident immune cells. ...

OBJECTIVE The goal of this study was to explore the role of Toll-like receptor 4 (TLR4) in vein graft remodeling and disease. METHODS AND RESULTS First, expression of TLR4 was analyzed in freshly isolated human saphenous veins (huSV), in freshly isolated huSV ex vivo perfused in an extracorporeal circulation, or in huSV used as coronary vein grafts. Marked induction of focal TLR4 expression w...

Agonist-induced dimerization of TLR4 Toll/IL-1R (TIR) domains initiates intracellular signaling. Therefore, identification of the TLR4-TIR dimerization interface is one key to the rational design of therapeutics that block TLR4 signaling. A library of cell-permeating decoy peptides, each of which represents a nonfragmented patch of the TLR4 TIR surface, was designed such that the peptides entir...

Toll-like receptor (TLR) 4 is the first identified mamalian homolog of the Drosophila Toll protein.1 TLR4 recognizes bacterial lipopolysaccharide (LPS), and also senses endogenous ligands including hyaluronic acid, oxidized low-density lipoprotein, and heat-shock proteins. Engagement of TLR4 with its ligand triggers a cascade of cellular signals through the intracellular signal transduction dom...

Objective We previously reported that dexmedetomidine (DEX) offers cardioprotection against ischemia/reperfusion injury in rats. Here, we evaluated the role of toll-like receptors 4- (TLR4-) myeloid differentiation primary response 88- (MyD88-) nuclear factor-kappa B (NF-κB) signaling in DEX-mediated protection of cardiomyocytes using in vitro models of hypoxia/reoxygenation (H/R). Methods Th...