What is Pam3CSK4?
Pam3CSK4 (Pam3CysSerLys4) is a synthetic triacylated lipopeptide (LP) and a TLR2/TLR1 ligand. It is a potent activator of the pro-inflammatory transcription factor NF-κB [1, 2]. Pam3CSK4 mimics the acylated amino terminus of bacterial LPs.
What does TLR2 recognize?
TLR2 recognizes a variety of microbial components derived from Gram-positive bacteria, such as lipopeptides, peptidoglycan, and lipoteichoic acids. TLR2 forms a heterodimeric complex with TLR1 or TLR6 to discriminate among different types of synthetic lipopeptides [82,83].
What are TLR ligands?
Endogenous TLR ligands are a group of molecules derived from host tissues or cells, either components of cells or induced gene products in specific conditions. These so-called endogenous TLR ligands and their receptors are localized in different cellular compartments and cannot interact physiologically.
Do macrophages have toll like receptors?
TLRs are expressed in innate immune cells such as dendritic cells (DCs) and macrophages as well as non-immune cells such as fibroblast cells and epithelial cells.
What does TLR5 bind to?
TLR5 is the only protein-binding TLR that is conserved in vertebrates from fish to mammals (7-9). TLR5 responds to a monomeric form of flagellin from β- and γ-proteobacteria that constitutes the whip-like flagellar filament responsible for locomotion (8, 10-11).
What is a TLR2 6 agonist?
We find that TLR2 and TLR6 are widely expressed on human melanoma cells, and that TLR2/6 agonists (MALP-2 or FSL-1) synergize with interferon-gamma (IFNγ) to induce production of CXCL10 from melanoma cells.
Are TLRs PRRs?
Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that initiate the innate immune response by sensing conserved molecular patterns for early immune recognition of a pathogen (1).
What does TLR 4 do?
Toll-like receptor 4 (TLR4) belongs to the family of pattern recognition receptors (PRRs). They are highly conserved receptors that recognize conserved pathogen-associated molecular patterns (PAMPs), thus representing the first line of defense against infections.
What happens to macrophages after they activate Toll-like receptors?
In response to an immune challenge, macrophages become activated and produce proinflammatory mediators that contribute to nonspecific immunity. The role of Toll-like receptors and transcription factors such as nuclear factor kappa B (NFκB) in the innate immune response is also described.
What does TLR5 do?
TLR5 recognizes bacterial flagellin, a principal component of bacterial flagella and a virulence factor. The activation of this receptor mobilizes the nuclear factor NF-κB and stimulates tumor necrosis factor-alpha production.
Is flagellin a protein?
Flagellin is a subunit protein of the flagellum, a whip-like appendage that enables bacterial motility.
How is the electrochemical detection of Pam3CSK4 performed?
Electrochemical detection of Pam3CSK4, a synthetic triacylated lipopeptide that mimics the structural moieties of its natural Gram negative bacterial pathogen-associated molecular pattern (PAMP) counterpart, has been achieved using hybridized toll-like receptors (TLR) combining TLR1 and TLR2 onto a single sensor surface.
What is the role of Pam3CSK4 in bacterial LPS?
Pam3CSK4 is a synthetic triacylated lipopeptide (LP) that mimics the acylated amino terminus of bacterial LPs. Pam3CSK4 is a potent activator of the proinflammatory transcription factor NF-κB. Activation is mediated by the TLR2/TLR1 heterodimer, which recognizes LPs with three fatty acids, a structural characteristic of bacterial LPs.
How is the NF-κB response of Pam3CSK4 determined?
Pam3CSK4 induces a dose-dependent response in HEK-Blue™ hTLR2 cells. These cells were stimulated with increasing concentrations of Pam3CSK4. After overnight incubation, the NF-κB response was determined using HEK-Blue™ Detection, a SEAP detection medium, and by reading the optical density (OD) at 630 nm.
How is Pam3CSK4 recognized by TLR2 and TLR1?
Recognition of Pam3CSK4, a triacylated LP, is mediated by TLR2 which cooperates with TLR1 through their cytoplasmic domain to induce the signaling cascade leading to the activation of NF-κB .