TLR 激活剂
TLR agonist
TLR1/2 Synthetic Triacylated Lipoproteins, Pam3CSK4 10ug/ml
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.
Specifically, the TLR2/TLR6 heterodimer detects diacylated lipoproteins, whereas the TLR2/TLR1 heterodimer recognizes triacylated lipoproteins.
TLR2 Peptidoglycan (PGN) 10ug/ml
Peptidoglycan (PGN) is a major surface component of Gram-positive bacteria. It is embedded in a relatively thick cell wall and is usually covalently attached to other polymers, such as lipoproteins and LTAs.
PGN is known to be a potent activator of NF-κB and TNF-α through TLR2.
However, other pattern recognition proteins have been reported to mediate the immunostimulatory activity of PGN.
Toll-like receptor 2 (TLR2) recognizes cell-wall components such as di- and triacylated lipoproteins from Gram-negative and Gram-positive bacteria, lipoteichoic acid from Gram-positive bacteria only, lipoarabinomannan from mycobacteria, and zymosan from yeast.
TLR2 Lipoteichoic Acid (LTA)
Lipoteichoic acid (LTA) is a major immunostimulatory component of Gram-positive bacteria.
Like LPS, LTA is an amphiphile formed by a hydrophilic polyphosphate polymer linked to a neutral glycolipid.
LTA stimulates immune cells through TLR2 to produce TNF-α and other inflammatory cytokines.
Recognition of LTA involves also LPS-binding protein (LBP) and CD14.
TLR2/6 Diacylated Lipoprotein (FSL-1) 10ug/ml
FSL-1 (Pam2CGDPKHPKSF) is a synthetic lipopeptide derived from Mycoplasma salivarium. It contains the same diacylglycerol structure as MALP-2 from M. fermentans but has a different peptide sequence.
The mycoplasmal lipopeptide FSL-1 contains a diacylated cysteine residue and is recognized by the TLR2/TLR6 heterodimer.
TLR4 Lipopolysaccharide (LPS) 1ug/ml
LPS-PG is a purified preparation of lipopolysaccharide (LPS) from the Gram-negative bacteria Porphyromonas gingivalis. LPS-PG is an important virulence factor in the mechanisms of peridontal disease. LPS is the principal component of Gram negative bacteria that activates the innate immune system.
LPS recognition is predominantly mediated by TLR4 [1]. The TLR4 response to LPS-PG is dependent on the presence of key accessory molecules, CD14 and MD2 [2].
LPS-PG presents a unique and heterogenous chemical structure, which differs from traditionally recognized enteric bacterium-derived LPS. The fact that LPS-PG exhibits activity in C3H/HeJ mice, which are deficient for TLR4, led to a common belief that this LPS is a TLR2 ligand [3, 4].
However, structural and functional studies of LPS-PG have revealed that it activates cells through TLR4.
The TLR2 activity of LPS-PG is ascribed to a contaminant lipoprotein [5].
TLR5 Flagellin 10ug/ml
Toll-like receptor 5 (TLR5) recognizes flagellin from both Gram-positive and Gram-negative bacteria. Activation of the receptor stimulates the production of proinflammatory cytokines, such as TNF-α, through signaling via the adaptor protein MyD88.
TLR5 can generate a proinflammatory signal as a homodimer suggesting that it might be the only TLR participating in flagellin recognition. However, TLR5 may require the presence of a co-receptor or adaptor molecule for efficient ligand recognition and/or signaling.
TLR3 Polyinosinicpolycytidylic Acid, polyI:C 50ug/ml
Polyinosinic-polycytidylic acid (usually abbreviated as poly(I:C) or poly(rI):poly(rC)) is a synthetic analog of double-stranded RNA (dsRNA), pathogen-associated molecular pattern (PAMP) associated with viral infection. Poly(I:C) is recognized by the antiviral pattern recognition receptors TLR3, RIG-I/MDA5 and PKR, thereby inducing signaling via multiple inflammatory pathways, including NF-kB and IRF.
TLR7 Imiquimod (R837) 10ug/ml
TLR7 Agonist – Imidazoquinoline compound
Imiquimod (R837), an imidazoquinoline amine analog to guanosine, is an immune response modifier with potent indirect antiviral activity.
The antiviral activity of imiquimod was first shown in guinea pigs infected with herpes simplex virus [1].
Imiquimod is now an approved treatment for external genital warts caused by human papillomavirus infection.
This low molecular synthetic molecule induces the production of cytokines such as IFN-α. Unlike R848, Imiquimod activates only TLR7 but not TLR8 [2].
This activation is MyD88-dependent and leads to the induction of the transcription factor NF-κB [3].
Unlike other commercially available Imiquimod preparations, InvivoGen’s Imiquimod for research is controlled for TLR7 potency and TLR4/TLR2 contamination.
TLR7/8 Single-Stranded RNAs 10ug/ml
Single-stranded RNA (ssRNA) has been identified as the natural ligand of TLR7 and TLR8 [1, 2].
ssRNA derived from HIV-1 or the influenza virus were shown to induce the production of proinflammatory cytokines in pDC [3, 4].
This induction was reproduced using polyU or GU-rich (ssRNA40) ODNs complexed with cationic lipids to protect them from degradation.
Upon stimulation with ssRNA, murine TLR7 and human TLR8 induced the activation of NF-κB, whereas human TLR7 and murine TLR8 failed, implying a species specificity difference in ssRNA recognition.
All ssRNAs/ORNs have been tested using HEK-Blue™ TLR7 and HEK-Blue™ TLR8 Cells to confirm their specificity.
TLR9 Type C CpG oligonucleoatide (C-CpG-ODN) 10ug/ml
CpG ODNs are synthetic oligonucleotides that contain unmethylated CpG dinucleotides in particular sequence contexts (CpG motifs).
These CpG motifs are present at a 20-fold greater frequency in bacterial DNA compared to mammalian DNA.
CpG ODNs are recognized by Toll-like receptor 9 (TLR9) leading to strong immunostimulatory effects.
ODN M362 is a CpG ODN class C specific for human / mouse TLR9.
C-class CpG ODNs contain a complete phosphorothioate backbone and a CpG-containing palindromic motif.
Class C CpG ODNs induce strong IFN-α production from pDC and B cell stimulation.