The IL18 Knockout 769-P Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 769-P human clear cell renal adenocarcinoma line, with targeted disruption of the IL18 gene. This heterogeneous cell pool provides a loss-of-function model for studying IL-18-mediated signaling without clonal selection artifacts. It is supplied as a ready-to-use resource for biochemical, cell-based, and immunological investigations.
The 769-P parental line is a primary clear cell renal adenocarcinoma model, widely employed in renal cell carcinoma (RCC) research due to its retention of key oncogenic features, including constitutive HIF pathway activation and relevant growth factor dependencies. As an adherent epithelial line, 769-P cells are suited for producing disease-relevant knockout derivatives to dissect tumor-intrinsic roles of inflammatory mediators such as IL-18.
IL-18 is an IL-1 family cytokine that bridges innate and adaptive immunity. Synthesized as an inactive precursor, it is cleaved by caspase-1 downstream of the NLRP3 inflammasome, which is activated by upstream signals like IL-1??, TNF-??, and LPS. Secreted IL-18 binds the IL-18R heterodimer, recruiting MyD88 and IRAK4, which phosphorylate IRAK, leading to TRAF6 oligomerization. TRAF6 activates TAK1, which stimulates the IKK complex and MAPK kinases, driving NF-??B nuclear translocation and JNK/p38 MAPK phosphorylation. Downstream, this cascade triggers transcription of IFN-??, Th1 cytokines, ICAM-1, VCAM-1, and chemokines such as CCL2 and CXCL8. Signaling is negatively regulated by IL-18BP and SIGIRR. In the knockout cells, the absence of IL-18 eliminates this signaling cascade, preventing NF-??B and MAPK activation and attenuating proinflammatory mediator output.
Within the 769-P RCC context, IL-18 can sustain an inflammatory microenvironment that promotes tumor progression and immune modulation. This knockout model enables dissection of IL-18??s contributions to cancer cell-autonomous phenotypes, such as proliferation, migration, and invasive capacity, as well as its impact on immune cell recruitment and Th1 polarization. It thus helps illuminate how IL-18 signaling influences renal carcinoma biology.
This polyclonal knockout population is advantageous for mechanistic studies employing Western blot for phospho-NF-??B/p65 and phospho-p38 MAPK, ELISA for IL-18 and IFN-?? secretion, and RT-qPCR for IL18 transcript analysis. It also supports functional assays like proliferation, migration, and invasion, drug screening for IL-18 pathway inhibitors, and co-culture systems to assess Th1 immune modulation. The cells facilitate inflammasome biology research and translational studies targeting IL-18 in RCC. For further information, technical support, or to order, please contact Ascent Research.
