The IL17RB Knockout 786-O Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population targeting the human IL17RB gene. This gene encodes the interleukin-17 receptor B, a cytokine receptor for IL-17B and IL-25. The knockout model is generated through CRISPR/Cas9-mediated disruption of the target gene in the 786-O host cell line, resulting in a heterogeneous cell pool with loss-of-function mutations. This polyclonal format captures the natural genetic diversity of the edited population, making it suitable for studying IL-17 receptor signaling in renal carcinoma contexts.
The 786-O cell line is an established human renal cell adenocarcinoma model derived from a primary clear cell renal cell carcinoma. These epithelial cells harbor a VHL deficiency, which leads to constitutive activation of hypoxia-inducible factor (HIF) and mimics the pseudohypoxic state characteristic of clear cell renal cell carcinoma. The VHL-deficient background drives angiogenic and metabolic reprogramming, providing a clinically relevant platform to investigate tumor-promoting signaling pathways. This host cell line is widely used in cancer biology to dissect the molecular mechanisms underlying renal tumorigenesis and to evaluate therapeutic interventions.
IL17RB functions as a receptor subunit for the cytokines IL-25 and IL-17B, typically forming heterodimers with the IL17RA chain to initiate intracellular cascades. Upon ligand binding, the receptor recruits the adaptor protein Act1 (TRAF3IP2) and the E3 ubiquitin ligase TRAF6, which in turn activate downstream effectors including the IKK complex, NF-??B, and MAP kinases such as MAPK3/1. This signaling axis also engages the JAK-STAT pathway, in particular STAT3, to drive transcriptional programs that upregulate pro-inflammatory mediators. Key targets include NFKBIA, CXCL8, IL6, CCL20, and the angiogenic factor VEGFA.
In the 786-O renal carcinoma background, disruption of IL17RB abrogates response to IL-25 and IL-17B, blocking assembly of the IL17RB/IL17RA receptor complex and preventing Act1/TRAF6-mediated signal propagation. This attenuates NF-??B and MAPK pathway activity, diminishing the expression of inflammatory cytokines and angiogenic drivers that are often aberrantly activated in clear cell renal cell carcinoma. Because 786-O cells already exhibit constitutive HIF activation, the knockout creates a valuable model for untangling the specific contributions of IL-17 receptor signaling versus hypoxia-driven pathways in tumor progression, metastasis, and microenvironmental modulation.
These polyclonal knockout cells support a wide range of experimental workflows to interrogate IL-25/IL-17B signaling in cancer biology. Western blotting and phospho-signaling analysis assess pathway activation, while RT-qPCR, ELISA, and flow cytometry quantify cytokine expression and receptor profiles. Functional assays such as proliferation, migration, and invasion studies evaluate the role of IL17RB in tumor cell behavior, and co-immunoprecipitation reveals protein interactions within the signaling complex. NF-??B luciferase reporter assays provide a direct transcriptional readout. Applications extend to drug target validation and receptor antagonist screening for inflammatory and oncologic diseases. For further details, contact Ascent Research.
