The IL17RA Knockout SK-HEP-1 Polyclonal Cells provide a genetically disrupted loss-of-function model for the interleukin-17 receptor A (IL17RA) gene, generated via CRISPR/Cas9-mediated gene knockout in the SK-HEP-1 human hepatic adenocarcinoma cell line. Supplied as a polyclonal population, this product offers a heterogeneous pool of edited cells, enabling robust study of IL17RA-dependent signaling without the need for single-cell clonal isolation. The CRISPR/Cas9 system introduces targeted disruptions within the IL17RA locus, abolishing functional receptor expression and providing a versatile tool for dissecting IL-17-mediated pathways in a liver-derived epithelial context.
The parental SK-HEP-1 cell line originates from the ascitic fluid of a patient with liver adenocarcinoma and exhibits an epithelial morphology, characteristics that make it a widely utilized model for hepatic pathophysiology, cancer biology, and inflammatory signaling. As an adherent cell line of human origin, SK-HEP-1 retains key features of hepatic epithelial cells, including the expression of certain liver-specific markers and responsiveness to cytokine stimulation. This background is particularly relevant for investigating the intersection of inflammation and oncogenesis, as chronic inflammatory signals can promote tumor progression in the liver microenvironment.
IL17RA encodes the cognate receptor subunit for the pro-inflammatory cytokines IL-17A and IL-17F, which upon ligand binding form a heteromeric complex with IL-17RC to initiate intracellular signaling cascades. The receptor recruits the adaptor ACT1 (CIKS) and the E3 ubiquitin ligase TRAF6, triggering the activation of TAK1 and the IKK complex, which phosphorylate I??B??, leading to NF-??B nuclear translocation. Concurrently, TRAF6 activates the MAPK pathways, including ERK, JNK, and p38, which in turn regulate transcription factors such as C/EBP?? and AP-1. These signaling hubs transcriptionally upregulate a plethora of downstream effectors, including IL-6, IL-8 (CXCL8), CXCL1, CCL20, G-CSF, and GM-CSF, as well as antimicrobial peptides like ??-defensins and S100A calcium-binding proteins. This network orchestrates immune cell recruitment and sustains pro-inflammatory microenvironments in tissues.
In the context of the SK-HEP-1 hepatic adenocarcinoma background, IL17RA signaling assumes particular significance given the liver??s exposure to gut-derived inflammatory mediators and its role in systemic acute-phase responses. Perturbations in the IL-17 pathway have been implicated in hepatocellular carcinoma progression, fibrosis, and hepatitis-associated inflammation. This polyclonal knockout model thus enables investigation of IL17RA’s contribution to hepatocyte-like inflammatory responses, tumor?Cimmune interactions, and the potential for anti-IL-17 therapeutics to modify cancer-associated inflammation. Researchers can explore how loss of IL17RA alters cytokine profiles, chemokine secretion, and downstream signaling networks within a liver tumor cell environment.
The IL17RA Knockout SK-HEP-1 Polyclonal Cells are suitable for a broad array of functional studies, including western blotting to assess phosphorylation states of key pathway components such as IKK??/??, JNK, and p38, NF-??B luciferase reporter assays to quantify transcriptional activation, RT-qPCR for transcript-level changes in downstream cytokines, and ELISA-based measurement of secreted proteins like IL-6 and IL-8. Additionally, these cells can be employed in chemotaxis and migration assays to evaluate immune cell recruitment, as well as drug screening platforms for novel anti-inflammatory agents targeting the IL-17 axis. The polyclonal nature of the product captures population-level signaling variability, making it ideal for high-throughput and pooled loss-of-function screens. For further details, please contact Ascent Research.
