The DPP9 Knockout SK-HEP-1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 human cell line, engineered to disrupt the DPP9 gene. This mixed population provides a loss-of-function model for studying DPP9-dependent cellular processes without prior clone isolation.
The SK-HEP-1 host cell line originates from ascitic fluid of a male patient with liver adenocarcinoma and exhibits endothelial characteristics, including features of liver sinusoidal endothelial cells (LSECs). LSECs are fenestrated endothelial cells lining hepatic sinusoids, serving critical roles in blood filtration, macromolecule scavenging, and hepatic immune regulation through antigen presentation and tolerance induction.
DPP9 encodes a cytosolic dipeptidyl peptidase that cleaves N-terminal dipeptides from substrates, restraining NLRP1 inflammasome activity and contributing to the generation of MHC class I-presented peptides. In resting cells, DPP9 interacts with the FIIND domain of NLRP1, maintaining NLRP1 autoinhibition. Upon DPP9 loss, this tonic suppression is relieved, leading to spontaneous NLRP1 oligomerization with ASC and Caspase-1, resulting in pyroptosis and release of IL-1?? and IL-18. Concurrently, altered peptide trimming may modify the peptide repertoire loaded onto MHC class I molecules via TAP1/TAP2. Inflammatory stimuli such as IFN-?? and TNF-?? regulate DPP9 expression, integrating it into innate immune signaling.
In the context of SK-HEP-1 LSEC-like cells, DPP9 knockout offers a relevant system to investigate NLRP1-driven inflammation and antigen presentation in liver-resident endothelial cells. LSECs modulate hepatic immune tolerance and inflammation, and dysregulated inflammasome activity is implicated in hepatocellular carcinoma and viral hepatitis. This model thus enables exploration of how DPP9-dependent inflammasome control influences endothelial cell pyroptosis, immune crosstalk, and tumor microenvironment signals.
Researchers can employ this polyclonal knockout cell population to monitor Caspase-1 activation by Western blot or FAM-FLICA flow cytometry, quantify IL-1?? and IL-18 secretion via ELISA, and assess pyroptotic cell death through LDH release assays. Additional applications include profiling NLRP1 and IL1B transcript levels by RT-qPCR and evaluating MHC class I surface expression. This model supports DPP9 inhibitor screening and autoinflammatory disease research. For further details and ordering information, please contact Ascent Research.
