Toll-like receptors (TLRs) play important roles in induction of innate immune responses for both host defense against invading pathogens and wound healing after tissue injury. Since dysregulation of TLR-mediated immune responses is closely linked to many chronic diseases, modulation of TLR activation by small molecules may have therapeutic potential against such diseases. Expression of the majo...

LPS has a priming effect on various stimuli. For instance, LPS priming enhances the production of platelet-activating factor (PAF), a proinflammatory lipid mediator that is induced by PAF itself. Among various enzymes responsible for PAF biosynthesis, acetyl-coenzyme A:1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase is one of the enzymes activated by PAF receptor stimulation. In ...

We are under constant threats from pathogens. A failure to initiate an appropriate immune response will lead to an immunocompromised state. Our innate immune system could sense foreign nucleic acids from parasites, viruses, fungi and bacteria. This is achieved through pattern recognition receptors (PRRs) on innate cells such as macrophages that recognise different pathogen-associated molecular ...

Toll-like receptor 4 (TLR4) induces two distinct signaling pathways controlled by the TIRAP-MyD88 and TRAM-TRIF pairs of adaptor proteins, which elicit the production of proinflammatory cytokines and type I interferons, respectively. How TLR4 coordinates the activation of these two pathways is unknown. Here we show that TLR4 activated these two signaling pathways sequentially in a process organ...

The Toll-like receptors (TLRs) of the innate immune system detect host invasion by pathogens and initiate immune responses. All of the TLRs use the adaptor MyD88 to transduce a signal; however, two newly identified signaling molecules, TIRAP and TRIF, interact with a subset of the TLRs, suggesting a signaling specificity that may be relevant to the type of infection. Activation of the TRIF path...

Toll-like receptors (TLRs) have been established to play an essential role in the activation of innate immunity by recognizing specific patterns of microbial components. TLR signaling pathways arise from intracytoplasmic TIR domains, which are conserved among all TLRs. Recent accumulating evidence has demonstrated that TIR domain-containing adaptors, such as MyD88, TIRAP, and TRIF, modulate TLR...

Toll-like receptor signaling requires functional Toll/interleukin-1 (IL-1) receptor (TIR) domains to activate innate immunity. By producing TIR homologous proteins, microbes inhibit host response induction and improve their own survival. The TIR homologous protein TcpC was recently identified as a virulence factor in uropathogenic Escherichia coli (E. coli), suppressing innate immunity by bindi...

BACKGROUND Toll-Like Receptor 4 (TLR4) signaling mediates early inflammation after cold ischemia-reperfusion (I/R). We hypothesized that the TLR4 coreceptor CD14, the intracellular adaptor proteins myeloid differentiation factor 88 (MyD88) and TIR domain-containing-adaptor inducing IFNbeta (TRIF) would be required for cold I/R induced inflammation. High mobility group box 1 (HMGB1) is a putativ...

There has been growing interest in the role of viral infections and their association with adverse pregnancy outcomes. However, little is known about the impact viral infections have on the fetal membranes (FM). Toll-like receptors (TLR) are thought to play a role in infection-associated inflammation at the maternal-fetal interface. Therefore, the objective of this study was to characterize the...