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...

C-reactive protein (CRP) is considered to induce the inflammatory response during atherosclerosis. Toll-like receptor 4 (TLR4)-mediated inflammatory signaling has been shown to facilitate atherogenesis. It remains thoroughly unknown whether TLR4 mediates the proinflammatory effect of CRP. Thus, the study was designed to explore TLR4-related mechanism of proinflammatory effect of CRP in rat vasc...

Toll-like receptors (TLR) play an essential role in the innate recognition of microorganisms by the host. To determine the role of TLR4 in host defense against lung tuberculosis, TLR4 mutant (C3H/HeJ) and wild-type (C3H/HeN) mice were intranasally infected with live Mycobacterium tuberculosis. TLR4 mutant mice were more susceptible to pulmonary tuberculosis, as indicated by a reduced survival a...

Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila Toll, a leucine-rich repeat molecule that can trigger innate responses against pathogens. The TLR4 gene has recently been shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS. However, transfection of TLR4 does not confer LP...