Neutrophils are the first immune cells to migrate into infected tissue sites. Therefore an important step in the initiation of an immune response is the synthesis of the neutrophil-recruiting chemokines. In this in vivo study in mice, we show that resident tissue macrophages are the source of the major neutrophil chemoattractants, KC and MIP-2. Synthesis of these chemokines is rapidly regulated...

Inflammatory pain can be triggered by different stimuli, such as trauma, radiation, antigen and infection. In a model of inflammatory pain caused by infection, injection in the mice paw of lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist, produces mechanical hyperalgesia. We identify here the TLR4 linked signaling pathways that elicit this response. Firstly, LPS paw injection in ...

In a 1984 review, Shlomo Eisenberg1 wrote, “In spite of their large number in plasma, it is difficult to define HDL as a vehicle for lipid transport ... other considerations must apply to this lipoprotein.” In this issue of Circulation, Suzuki et al2 report that high-density lipoprotein (HDL) suppresses the type I interferon response in macrophages challenged with lipopolysaccharide. They found...

Graft-versus-host disease (GVHD) is initiated by APCs that prime alloreactive donor T cells. In antipathogen responses, Ag-bearing APCs receive signals through pattern-recognition receptors, including TLRs, which induce the expression of costimulatory molecules and production of inflammatory cytokines, which in turn mold the adaptive T cell response. However, in allogeneic hematopoietic stem ce...

Administering high levels of inspired oxygen, or hyperoxia, is commonly used as a life-sustaining measure in critically ill patients. However, prolonged exposures can exacerbate respiratory failure. Our previous study showed that TLR4 confers protection against hyperoxia-induced lung injury and mortality. Hsp70 has potent cytoprotective properties and has been described as a TLR4 ligand in cell...

Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF) is an adaptor molecule that is recruited to TLR3 and -4 upon agonist stimulation and triggers activation of IFN regulatory factor 3 (IRF3) and expression of type 1 IFNs, which are critical for cellular antiviral responses. We show that Akt is a downstream molecule of TRIF/TANK-binding kinase 1 (TBK1) and plays an important role in the a...

Lipopolysaccharide (LPS) induced-vascular inflammation plays a central role in vasculitis and atherosclerosis. The stimulation of toll-like receptor 4 (TLR4) by LPS elicits the release of major proinflammatory cytokines that aggravates cardiovascular disorders. Peroxisome proliferator- activated receptor alpha (PPARalpha) agonists have been shown to reduce cardiovascular events by controlling l...

Despite its presence on resident skin cells, the role of TLR4 in skin diseases remains poorly understood. This is highly significant because the skin biome is rich with potential TLR4 agonists. We aimed to establish the contribution of TLR4 to atopic dermatitis and determine the mechanism by which TLR4 acts in an experimental model of atopic dermatitis. MyD88, TLR4, or Toll-IL-1R domain-contain...

The use of Adenovirus (Ad)-based vectors has proven to be a useful platform for the development of gene therapy and vaccine protocols. The immunological mechanisms underlying these properties need to be identified and understood to foster safer, more efficacious use of this important gene transfer platform. Our recent studies have confirmed an important role for MyD88 dependent toll-like recept...

Aim. To gain an insight into the effect of HCV replication-associated interference with the IFN system on hepatic mRNA expression involved in IFN production. Methods. Relative mRNA expression of TLR3/RIG-I signaling genes involved in IFN- β production was correlated with positive- and negative-strand HCV RNAs in pretreatment liver tissues responsive and nonresponsive to peginterferon and ribavi...