The IL1R1 Knockout A2780 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal population of human ovarian carcinoma epithelial cells with targeted disruption of the IL1R1 gene, eliminating expression of the interleukin-1 receptor type 1 (IL1R1). This loss-of-function knockout model disables the primary receptor for the pro-inflammatory cytokines IL-1?? and IL-1??, providing a robust tool for studying IL-1 signaling without clonal selection biases. The polyclonal format ensures a heterogeneous knockout pool, enabling physiologically relevant investigations.
The A2780 host cell line is an adherent epithelial line derived from an untreated patient with ovarian endometrioid adenocarcinoma, retaining tumorigenic properties and widely used in ovarian cancer research, particularly in studies of drug resistance. These cells serve as a relevant platform for examining how IL-1 signaling contributes to ovarian tumor biology and therapeutic responses.
IL1R1 functions as the high-affinity receptor for IL-1?? and IL-1??; ligand binding induces heterodimerization with IL-1RAP and recruitment of the adaptor MyD88. This triggers IRAK4 and IRAK1 kinases, activating TRAF6, which in turn stimulates TAK1-mediated activation of the IKK complex and MAPK cascades (JNK, p38). Downstream, NF-??B and MAPKs drive transcription of pro-inflammatory genes including IL6, IL8, PTGS2 (COX-2), MMPs, and ICAM1. The pathway is regulated by upstream factors such as TNF-??, LPS, and the endogenous antagonist IL-1Ra. IL1R1 knockout ablates this entire signaling axis, preventing induction of these effectors.
In ovarian cancer, IL-1 signaling promotes a tumor-permissive microenvironment, enhances inflammation, and contributes to chemoresistance. Eliminating IL1R1 in A2780 cells creates a powerful model to dissect the role of IL-1 pathways in inflammation-driven ovarian tumor progression and drug resistance mechanisms. This model is also relevant to understanding cancer-related inflammation in autoinflammatory diseases such as CAPS, rheumatoid arthritis, and inflammatory bowel disease.
These knockout cells enable detailed functional studies: IL-1??-induced NF-??B reporter assays can confirm pathway inactivation; western blotting for phospho-p65 and I??B?? quantifies signaling blockade; ELISA and cytokine profiling detect reduced secretion of IL-6 and IL-8. RT-qPCR can measure expression changes of IL-1 targets, while Transwell assays assess migration/invasion. Cell viability studies evaluate drug sensitivity, and co-culture with immune cells explores tumor-immune interactions. They are ideal for screening IL-1 pathway inhibitors and validating immuno-oncology targets. For additional information, contact Ascent Research.
