The IL1RN Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the IL1RN gene in the human NCI-H1975 lung adenocarcinoma epithelial cell line. This product provides a heterogeneous polyclonal pool of cells harboring target-gene disruption, serving as a loss-of-function model to investigate the biological role of the interleukin-1 receptor antagonist (IL-1RA) in cancer and inflammatory signaling. The polyclonal format eliminates the need for single-cell cloning, offering a representative population for functional studies without the clonal selection bias inherent in monoclonal isolates. Researchers can use these cells to study IL1RN-dependent pathways in a clinically relevant NSCLC background.
The host cell line, NCI-H1975, is derived from a human female with non-small cell lung cancer (NSCLC) of adenocarcinoma subtype. It is a well-characterized model harboring EGFR L858R and T790M mutations, which confer sensitivity to first-generation EGFR tyrosine kinase inhibitors (TKIs) and secondary resistance through the T790M gatekeeper mutation. This genetic background makes NCI-H1975 a key platform for investigating mechanisms of acquired drug resistance, tumor progression, and the impact of the tumor microenvironment on therapeutic response. The adherent epithelial morphology and stable growth characteristics facilitate reproducible in vitro assays.
IL1RN encodes IL-1RA, a competitive antagonist that binds the IL-1 receptor type 1 (IL-1R1) without inducing signal transduction, thereby blocking IL-1?? and IL-1??-mediated activation of the NF-??B and MAPK signaling cascades. IL-1RA competes with IL-1?? and IL-1?? for IL-1R1 binding and also interacts with IL-1R2 and the co-receptor IL-1RAcP. Under inflammatory conditions, IL1RN expression is upregulated by transcription factors such as NF-??B and HIF1A, as well as by stimuli like LPS and corticosteroids. Disruption of IL1RN is predicted to remove this inhibitory checkpoint, leading to unopposed IL-1R1 engagement and hyperactivation of downstream pathways involving IRAK1, TRAF6, JNK, and p38 MAPK, ultimately promoting transcription of pro-inflammatory cytokines (e.g., IL-6, IL-8, TNF-??), chemokines, and matrix metalloproteinases. Thus, the knockout model allows dissection of IL-1 feedback regulation and its downstream effector networks.
In the NCI-H1975 background, IL1RN knockout is expected to amplify IL-1 signaling, which may influence cell proliferation, apoptosis, and the production of an inflammatory secretome. Given the EGFR mutant status, this model enables investigation of crosstalk between oncogenic EGFR signaling and the IL-1/NF-??B/MAPK axis, potentially uncovering mechanisms by which inflammatory pathways modulate drug resistance. The polyclonal knockout population is particularly suitable for studying heterogeneous tumor cell responses and for screening experiments where clonal uniformity is not required, such as cytokine profiling or drug combination testing. The interplay between IL-1RA loss and the EGFR-driven signaling landscape provides a unique tool for exploring how the inflammatory milieu contributes to NSCLC progression and therapeutic escape.
This knockout product has broad applications in immuno-oncology, tumor microenvironment research, inflammatory signaling, and cytokine biology. Representative experimental workflows include Western blotting and RT-qPCR to confirm IL1RN disruption and assess downstream target expression; ELISA and cytokine arrays to quantify secreted factors; NF-??B reporter assays to monitor pathway activity; and functional assays such as cell viability, migration, invasion, and drug sensitivity profiling. The cells are suitable for co-culture systems, 3D spheroid models, and in vivo xenograft studies to evaluate the impact of IL-1RA deficiency on tumor-immune interactions and response to therapy. For additional product details, custom gene editing, or technical support, please contact Ascent Research.
