| 包装: | 1mg |
| 市场价: | 2489元 |
Cell lines | HepaRG cell |
Preparation Method | Indicated differentiated HepaRG cell lines were infected with HBV with 100 vge/cell. At day-7 post-infection , cells were treated twice with either Pam3CSK4 (100 ng/mL), IFNα (500 IU/mL), RG7834 (0.1 μM), or the nucleoside analogue lamivudine (3 TC; 1 μM) for a total exposure time of 6 days. Cells and supernatants were harvested for analyses at day-13 post-infection. |
Reaction Conditions | 100 ng/mL; 6 days |
Applications | Pam3CSK4 was capable to inhibit HBV (genotype D) replication in dHepaRG cells. The levels of all HBV parameters analyzed, (including intracellular total HBV RNAs, viremia, and secretion of viral antigens) were significantly reduced even at very low concentration of Pam3CSK4. Pam3CSK4 was also capable to inhibit the replication of another HBV genotype (genotype C). thus suggesting a broad antiviral activity against HBV. Pam3CSK4 as a TLR2 agonist, is a potent anti-HBV agents. Pam3CSK4 inhibits RNA accumulation by both impairing HBV transcription and RNA stability. Pam3CSK4 decreases also cccDNA level via a FEN-1-dependent mechanism. |
Animal models | C57 BL/6 mice |
Preparation Method | To analyse the influence of TLR2 heterodimer activation on IL-13-induced itch-like behaviour, C57 BL/6 mice were pre-administered with Pam3CSK4 (20 μg/100 μl sterilized water) by gavage every three days for 3 times . In another experiment, FSL-1 (0.3 mg/kg, 60 μl sterilized water) was intraperitoneally injected 14 h before IL-13 injection. Control mice were given sterilized water only. All of these mice were then intradermally injected with IL-13 (1 μg/10 μl) or vehicle into the left cheek. All the mice were video-recorded for 1 h for the analysis of scratching bouts. |
Dosage form | Pam3CSK4 (20 μg/100 μl sterilized water) by gavage every three days for 3 times |
Applications | As a cutaneous regulator, IL-13 activates sensory neurons and participates in the initiation of AD and itch. Pam3CSK4 enhances IL-13-induced calcium transient in sensory neurons and elevates IL-13-induced Itch-like behaviours in mice。 |
| 产品描述 | Pam3CSK4 (Pam3CysSerLys4) is a synthetic triacylated lipopeptide (LP) and a TLR2/TLR1 ligand agonist with an EC50 of 0.47 ng/mL[10]. Pam3CSK4 mimics the acylated amino terminus of bacterial LPs. Bacterial LPs are a family of pro-inflammatory cell wall components found in both Gram-positive and Gram-negative bacteria. These bacterial LPs are recognized by TLR2, a receptor that plays a pivotal role in detecting a diverse range of pathogen-associated molecular patterns (PAMPs).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[1]. In HepaRG cells, Pam3CSK4 shows a broad antiviral activity against HBV. Pam3CSK4 is a well-characterized and specific TLR1/2 ligand[2]. The anti-HBV effect of Pam4CSK4 is dependent on TLR1/2 and its adaptor MyD88, targeting TLR1 or TLR6 with specific siRNA do affect the feed-forward expression of TLR2 in the context of Pam3CSK4 activation ; but invalidation of TLR1 led to a reduced inhibitory effect of Pam3CSK4. The low functional level of TLR2 was sufficient to produce the therapeutic effect of Pam3CSK4[4,5].Thus confirming that Pam3CSK4 likely signals through TLR1/2 heterodimers in hepatocytes[3]. Activation of TLR2/1 heterodimers by Pam3CSK4 mediates pain and itching, whereas activation of TLR2/6 heterodimers by lipoteichoic acid (LTA) or yeast glycan leads to itching[9]. As a cutaneous regulator, IL-13 activates sensory neurons and participates in the initiation of AD and itch[7]. IL-13 alone did not lead to a significant increase in scratching number，TLR2 promotes IL-13 signaling in sensory neurons. Innate TLR2 signaling not only promotes itch and pain but convert transient TH2 cell-mediated dermatitis into persistent inflammation which is linked to chronic human AD[8]. In mice pretreated with Pam3CSK4, IL-13 injection caused approximately twice as many scratches as vehicle injection[6]. Pam3CSK4 enhances IL-13-induced calcium transient in sensory neurons and elevates IL-13-induced Itch-like behaviours in mice. [1]: Ozinsky A, Underhill DM, et,al.The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13766-71. doi: 10.1073/pnas.250476497. PMID: 11095740; PMCID: PMC17650. |
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