The IL1RAP Knockout SK-HEP-1 Polyclonal Cells comprise a genetically heterogeneous population of SK-HEP-1 cells in which the IL1RAP gene has been disrupted by CRISPR/Cas9-mediated genome editing. This polyclonal knockout model provides a powerful tool for loss-of-function studies of the interleukin-1 receptor accessory protein (IL1RAP) in a human hepatic endothelial context, preserving population-level heterogeneity for robust functional analysis.
The parental SK-HEP-1 cell line was originally derived from a human liver adenocarcinoma and retains many phenotypic characteristics of liver sinusoidal endothelial cells (LSECs). LSECs are specialized endothelial cells that line the hepatic sinusoids and play critical roles in filtration, immune surveillance, and the regulation of hepatic inflammation. SK-HEP-1 cells are widely employed as an in vitro model system to investigate endothelial cell biology, hepatic immune responses, and the tumor microenvironment.
IL1RAP serves as an obligate co-receptor for the pro-inflammatory cytokines interleukin-1 (IL-1??/??), interleukin-33 (IL-33), and interleukin-36 (IL-36). Upon ligand engagement, IL1RAP heterodimerizes with the specific binding receptors IL1R1, ST2 (IL1RL1), and IL1RL2, respectively. The intracellular TIR domains recruit the adaptor MyD88 and the kinases IRAK1 and IRAK4, leading to TRAF6-dependent activation of the IKK complex and MAPK cascades. This results in the nuclear translocation of NF-??B and activation of JNK and p38, which drive the transcriptional induction of pro-inflammatory genes such as IL6, TNF, and CXCL8.
In the hepatic context, IL1RAP-mediated signaling in LSECs contributes to liver inflammation, fibrosis, and tumor progression. The SK-HEP-1 knockout model facilitates the dissection of IL1RAP-dependent endothelial responses to IL-1, IL-33, and IL-36, enabling studies of leukocyte adhesion, cytokine secretion, and intracellular signaling in a physiologically relevant human cell system. It is a valuable tool for investigating the role of IL1RAP in hepatic diseases and for screening therapeutic candidates.
Researchers can utilize this polyclonal knockout population in a range of experimental workflows, including RT-qPCR for target gene expression, phospho-specific immunoblotting or ELISA for NF-??B and p38 activation, and co-immunoprecipitation to assess receptor complex assembly. Additional applications include NF-??B reporter assays, cytokine ELISA for downstream effectors (e.g., IL-6, TNF), and flow cytometric analysis of surface receptors. This product is designed for studies in cytokine signaling, liver immunology, and drug discovery. For technical inquiries or ordering information, please contact Ascent Research.
