The IL1R1 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited human gastric epithelial cell population in which the IL1R1 gene has been disrupted. This polyclonal knockout model provides a genetically heterogeneous loss-of-function platform for studying interleukin-1 (IL-1) receptor signaling in a disease-relevant background. The host AGS cell line, derived from a gastric adenocarcinoma, retains key epithelial properties and is widely used for gastric cancer and H. pylori infection research.
The AGS cell line is an adherent epithelial line isolated from a human gastric adenocarcinoma. It serves as a standard model for investigating gastric cancer biology and host-pathogen interactions with Helicobacter pylori, owing to its well-characterized epithelial phenotype and responsiveness to pro-inflammatory stimuli. This background is particularly suited for exploring the role of IL-1 signaling in gastric mucosal inflammation and tumorigenesis.
The IL1R1 gene encodes the IL-1 receptor type 1, which forms complexes with the co-receptor IL1RAP upon binding the ligands IL-1?? or IL-1??. This engagement recruits the adaptor protein MyD88, triggering a kinase cascade involving IRAK1, IRAK4, and the E3 ligase TRAF6. Downstream, the IKK complex activates NF-??B transcription factors (p65/p50), while parallel MAPK pathways (ERK, JNK, p38) are stimulated. These signals induce expression of pro-inflammatory targets such as NFKB1, RELA, JUN, FOS, IL6, IL8, and TNF. The pathway is counterbalanced by the decoy receptor IL1R2 and the antagonist IL1RN.
In AGS gastric epithelial cells, IL-1R1-mediated signaling couples extracellular inflammatory cues to transcriptional programs that promote cytokine production and tumorigenic behaviors. Disruption of IL1R1 abrogates cellular responses to IL-1??/IL-1??, eliminating downstream NF-??B and MAPK activation. This knockout model thereby enables precise investigation of how IL-1 contributes to gastric cancer cell proliferation, survival, and the inflammatory microenvironment exacerbated by H. pylori infection, offering insights into mechanisms of chronic inflammation-driven carcinogenesis.
Typical experimental applications include Western blot detection of phosphorylated p65 and ERK, RT-qPCR and ELISA for IL-6 and IL-8, and NF-??B luciferase reporter assays to quantify pathway activity. Additional techniques encompass immunofluorescence for p65 nuclear translocation, flow cytometry to confirm loss of surface IL1R1, and functional assays such as colony formation and migration studies. Researchers can use this polyclonal knockout model for drug target validation, screening of IL-1R1 pathway inhibitors, and mechanistic studies of immune evasion in gastric adenocarcinoma. For further information, please contact Ascent Research.
