The IL1R1 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human SK-HEP-1 hepatic adenocarcinoma line, featuring targeted disruption of the IL1R1 gene. This loss-of-function model ablates IL-1 receptor type I signaling, enabling precise dissection of IL-1-dependent pathways. The polyclonal population, generated via Cas9-mediated gene disruption without clonal selection, reduces clonal artifacts and offers a robust tool for functional studies, including ligand-stimulation and downstream signaling analyses.
SK-HEP-1 cells originate from a human liver adenocarcinoma and are extensively used in hepatic oncology research to study tumorigenesis, metastasis, and inflammation. Their retention of core signaling networks makes them a relevant host for modeling cytokine receptor biology within a clinically pertinent liver cancer background, ideal for investigating the intersection of inflammatory signaling and liver cancer progression.
IL1R1 encodes the type I interleukin-1 receptor, a central mediator of pro-inflammatory responses. Upon binding of upstream ligands IL-1?? or IL-1??, IL1R1 forms a complex with the co-receptor IL-1RAcP (IL1RAP), recruiting the adaptor MyD88 and activating kinases IRAK4 and TRAF6. This triggers the IKK complex and MAPK cascades, leading to NF-??B and AP-1 transcription factor activation. Downstream, expression of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-?? is upregulated. The receptor is negatively regulated by IL-1 receptor antagonist (IL-1Ra, IL1RN).
In SK-HEP-1 cells, IL1R1 knockout allows dissection of IL-1 signaling??s role in hepatic adenocarcinoma. Elevated IL-1 levels in the liver tumor microenvironment drive NF-??B-mediated gene expression that can promote tumor growth and immune evasion. Eliminating IL1R1 enables interrogation of altered downstream signaling, cytokine secretion, and cellular phenotypes, providing insights into inflammatory mechanisms in liver cancer and potential therapeutic targets.
Applications include Western blotting to confirm IL1R1 loss and assess phospho-I??B??, RT-qPCR for IL1R1 mRNA quantification, IL-1?? stimulation with NF-??B reporter assays, immunofluorescence for NF-??B nuclear translocation, and ELISA for IL-6 secretion. Flow cytometry for surface IL1R1 expression and viability assays under inflammatory conditions are also feasible. This model supports drug screening targeting IL1R1. For further details, contact Ascent Research.
