The ACOD1 Knockout LoVo Polyclonal Cells constitute a CRISPR/Cas9-edited human cell population in which the aconitate decarboxylase 1 (ACOD1/IRG1) gene has been disrupted. This polyclonal knockout model, derived from the LoVo colorectal adenocarcinoma cell line, provides a versatile loss-of-function system for investigating ACOD1-mediated immunometabolism and inflammatory signaling. The polyclonal format eliminates clonal selection artifacts while maintaining a heterogeneous knockout background suited for population-level assays such as cytokine profiling, metabolic flux analysis, and high-throughput screening.
The LoVo host cell line was established from a metastatic lymph node of a 56-year-old male with Dukes’ type C colorectal adenocarcinoma and exhibits epithelial morphology with metastatic potential. These cells serve as a well-characterized model for studying colorectal cancer progression, epithelial-to-mesenchymal transition, and tumor-immune system interactions. Their endogenous expression of pattern recognition receptors and responsiveness to inflammatory mediators such as LPS and TNF-?? render them valuable for probing ACOD1-related immunometabolic mechanisms in a colorectal cancer context.
ACOD1 encodes an enzyme that converts cis-aconitate to the immunomodulatory metabolite itaconate. Itaconate inhibits succinate dehydrogenase (SDH) to diminish succinate-driven reactive oxygen species and alkylates KEAP1 to trigger NRF2-mediated antioxidant transcription. It also restrains NLRP3 inflammasome assembly and covalently modifies GAPDH, ALDOA, gasdermin D, and Tet2. ACOD1 expression is powerfully upregulated by LPS, IFN-??, and TNF-?? via signaling through NF-??B, IRF1, STAT1, and type I interferon pathways, integrating innate immunity with metabolic control.
In LoVo colorectal adenocarcinoma cells, ACOD1 disruption is anticipated to abolish itaconate production, thereby dysregulating key immunometabolic checkpoints. Loss of itaconate-dependent SDH inhibition and NRF2 activation may alter the cellular redox balance, enhance succinate-driven inflammatory signaling, and sensitize cells to apoptotic or pyroptotic stimuli. This knockout model thus enables dissection of how ACOD1 shapes tumor-intrinsic inflammatory responses and metabolic reprogramming, potentially influencing processes relevant to colorectal cancer metastasis and the tumor microenvironment.
Researchers can employ these polyclonal ACOD1 knockout LoVo cells to study itaconate-mediated immunometabolic regulation, anti-inflammatory mechanisms, and NLRP3 inflammasome control. The model is applicable to bacterial infection mimetics, metabolic profiling, and drug target validation in inflammatory and oncologic contexts. Key compatible techniques are LC-MS/MS itaconate quantification, SDH activity assays, IL-1?? ELISA for inflammasome readouts, NRF2 target qPCR, NF-??B reporter assays, Western blotting, and functional assays for proliferation, migration, and apoptosis. For additional technical information, contact Ascent Research.
