Current Pharmaceutical Design - Volume 12, Issue 32, 2006

In higher vertebrates and in mammals Toll- like receptors (TLRs) represent a bridge between innate and adaptive immunity. In this respect, a number of recent studies have led to the discovery of various TLRs in mice and in men, as well as to the characterization of structure and function of these receptors. In virtue of TLR ability to trigger a cascade of inflammatory and regulatory events, they are currently investigated as Read More

In this paper we analyze a 55-amino acid (aa) sequence which is relatively well conserved in several seventransmembrane receptor families (from Insects to Mammals) and in some Viruses. This sequence, which covers the second transmembrane domain, the first extracellular loop and the third transmembrane domain, appears in its complete configuration in most of the seven-transmembrane receptor families, as well as i Read More

The identification of the TLRs as key sensors of microbial infection has presented a series of new targets for drug development. The TLRs are linked to the most powerful inflammatory pathways in mammals. The question arises from the start: do we wish to stimulate TLR signaling in order to eradicate specific infections and/or neoplastic diseases? Or do we wish to block TLR signaling to treat inflammatory diseases? If we acce Read More

Toll-like receptors (TLRs) are evolutionary conserved transmembrane proteins that recognize a unique pattern of molecules derived from pathogens or damaged cells, triggering robust but defined innate immune responses. TLRmediated innate and/or adaptive immune responses play an important role in a variety of diseases including infectious diseases, sepsis, autoimmune diseases, allergy, and atherosclerosis. Each Read More

Activation of macrophages through TLR4, the receptor for the bacterial endotoxin LPS, results in a potent inflammatory response aimed at eliminating the invading pathogen. Excessive production of inflammatory mediators is harmful to host tissue and in extreme cases can result in fatal outcomes. This inflammatory response is, therefore, tightly regulated by negative regulatory mechanisms that act to maintain hom Read More

Innate immunity responds to various pathogen-associated molecular patterns (PAMPs) to evaluate the biological nature of foreign materials by using limited numbers of receptors. Analyses of interactions between PAMPs and its receptors are essential to understand the molecular basis regarding how we discriminate self and non-self materials. Upon infection of horseshoe crabs, an arthropod species, rapid hemolymph c Read More

Toll-like receptors (TLRs) recognize common motifs, pathogen-associated molecular patterns (PAMPs), in microorganisms. Bacterial PAMPs are mainly distributed on cell-surfaces. Peptidoglycans (PGNs) are ubiquitous constituents of bacterial cell walls. Muramyldipeptide (MDP; N-acetylmuramyl-L-alanyl-D-isoglutamine) is a common and key structure of PGNs and exhibits most the of bioactivities of PGNs. Recently, Read More

Toll-like receptors (TLRs) have emerged as critical players in immunity. They are capable of sensing organisms ranging from protozoa to bacteria, fungi or viruses upon detection of the pathogen as well as recognizing endogenous ligands, and triggering transduction pathways. Following activation of the innate immune system, strong inflammatory signals are generated inducing inflammation and activation of the adaptiv Read More

The family of the toll-like receptors comprises a minimum of 10 members identified in humans so far. These transmembrane receptors act as important signaling intermediates between the host and the invading pathogens. The following review describes the complexities encountered by researchers studying toll-like receptor (TLR) expression changes during bacterial infections. Mutations in some of the TLRs, most promin Read More

Toll-like receptors (TLRs) have been identified as a major class of pattern-recognition receptors. Recognition of pathogen-associated molecular patterns (PAMPs) by TLRs, either alone or in heterodimerization with other TLR or non-TLR receptors, induces signals responsible for the activation of innate immune response. Recent studies have demonstrated a crucial involvement of TLRs in the recognition of fungal pathogens suc Read More

The mucosal immune system is equipped with unique innate and acquired defense mechanisms which provide a first line of protection against ingested and inhaled infectious agents. Peyer's patches (PPs) and nasopharynx-associated lymphoid tissue (NALT) have been shown to be important inductive sites for the initiation of the acquired phase of antigen- specific immune responses. In addition, the mucosal innate immune sy Read More

Toll-like receptors (TLRs) are sensors of microbial products that initiate host defense responses in multicellular organisms. They are mainly linked to innate immunity and bridging to adaptive immunity, signaling through different TLRs responsible for a wide range of biological responses. The intracellular signaling pathways through Toll/interleukin- 1 receptor (IL-1R) domains result in recruitment of the cytoplasmic adaptor mol Read More

Cardiovascular disease ranks among the leading causes of morbidity and mortality in adult populations in the Western world. Significant progress in understanding the etiology of cardiovascular disease has come from recent recognition that chronic inflammation plays a key role in its development. The principal mediators of this inflammatory response, and the mechanisms by which they work, however, are incomplet Read More

Dendritic cells (DCs) represent a bridge between innate and adaptive immunity, being the maturation process dependent on the binding of pathogen-associated molecular patterns (PAMPs) to Toll-Like Receptors (TLRs) expressed on their surface. TLRs associated to adaptor proteins, following binding to PAMPs, are able to skew specific immune responses towards the T helper (h)1- or the Th2-type according to the anti Read More

Dendritic cells (DCs), instructed by the priming signals from microbial factors, can produce interleukin (IL)- 12p70 and promote T helper (Th)1 proliferation and interferon (IFN)-γ production. This event seems to be critical for the containment of infections caused by intracellular pathogens, even including Leishmania infection. In the present in vitro study we have investigated: 1) phagocytic capacities and IL-12 production by Read More

Nowadays, infections with Candida albicans (C.a.) are very frequent, mostly in the so-called immunocompromised host. Therefore, research has been focused on the types of immune response elicited by C.a., with the aim to develop novel therapeutic strategies. Neutrophils and macrophages (M) are deeply involved in the host defense against C.a., and also dendritic cells (DCs) seem to be very active in the host protection. In Read More

Flavonoids have beneficial activities which modulate oxidative stress, allergy, tumor growth and viral infection, and which stimulate apoptosis of tumor cells. In addition to these activities, dietary flavonoids are able to regulate acute and chronic inflammatory responses. Here we describe new aspects of regulatory mechanisms by which flavonoids suppress production of tumor necrosis factor-α (TNF-α) by macrophages, microgl Read More