The CASP4 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the AGS human gastric adenocarcinoma cell line, featuring targeted disruption of the CASP4 gene. This loss-of-function model enables detailed investigation of CASP4-dependent biological processes in a gastric epithelial context, without the genetic homogeneity imposed by clonal selection, thus maintaining a polyclonal background reflective of heterogeneous tumor populations.
The AGS parental cell line, established from a 54-year-old female patient with gastric adenocarcinoma, serves as a well-characterized model for gastric cancer and epithelial biology. These cells are extensively used to study gastric carcinogenesis mechanisms, mucosal immune responses, and host-pathogen interactions. Their gastric epithelial origin provides a physiologically relevant system for examining innate immune pathways, particularly those involving inflammasome activation and pyroptotic cell death that contribute to gastric inflammation and cancer progression.
CASP4 functions as an intracellular sensor for lipopolysaccharide (LPS), mediating non-canonical inflammasome activation. Upon binding cytosolic LPS, CASP4 oligomerizes and directly cleaves gasdermin D (GSDMD), triggering pyroptotic cell death and the concomitant release of pro-inflammatory cytokines interleukin-1?? (IL-1??) and IL-18. CASP4 expression is induced upstream by LPS detection through Toll-like receptor 4 (TLR4), which signals via TRIF to promote type I interferon production and subsequent transcription of CASP4 by interferon regulatory factors IRF1 and IRF2. This pathway also interacts with NLRP3 inflammasome components and caspase-1, positioning CASP4 as a critical executor of inflammatory cell death. Consequently, disruption of CASP4 in this model abolishes LPS-triggered pyroptosis and cytokine secretion, providing a clean genetic background to delineate upstream regulators, downstream targets, and interacting factors.
In the gastric mucosa, CASP4-driven pyroptosis has been implicated in inflammation-associated gastric cancer progression and epithelial barrier disruption. The AGS knockout model allows researchers to dissect the cell-autonomous role of CASP4 in gastric epithelial inflammatory responses, elucidating how aberrant inflammasome activation contributes to gastric tumorigenesis. Moreover, this model is valuable for systemic inflammatory disease research, including sepsis and inflammatory bowel disease, where CASP4-mediated cytokine storm and pyroptosis are major pathological drivers. CASP4 dysregulation is also emerging in neurodegeneration, extending the utility of this knockout platform to neuroinflammation studies.
Typical experimental applications include monitoring LPS-induced pyroptosis by lactate dehydrogenase (LDH) release assays, detecting GSDMD cleavage by Western blotting, and quantifying IL-1?? and IL-18 secretion via ELISA. Confocal microscopy enables visualization of GSDMD pore formation, while RT-qPCR allows transcriptional profiling of inflammasome components and cytokines. These polyclonal knockout cells are well-suited for studies on innate immunity, pyroptosis mechanisms, LPS signaling, and gastric cancer inflammation, as well as broader investigations into inflammatory and neurodegenerative diseases. For further technical information or to place an order, please contact Ascent Research.
