Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by late diagnosis and a pro-inflammatory tumour microenvironment. Inflammation plays a central role in PDAC progression, with inflammasomes such as AIM2 and NLRP3 contributing to cytokine production and immune modulation. This study aimed to characterize the activity of the AIM2 inflammasome and alternative inflammatory signalling in three PDAC cell lines, AsPC-1, BxPC-3, and CFPAC-1, by evaluating the expression of inflammasome-related genes (AIM2, CASP1, PYCARD, IL1B, CASP8, NFKB1), inflammasome assembly, caspase activity, and cytokine secretion.
Gene expression analysis via qPCR revealed high transcriptional levels of AIM2 and the ASC-encoding gene PYCARD in BxPC-3 cells, which also exhibited AIM2/ASC protein co-localization via immunofluorescence and strong caspase-1 enzyme activity. In contrast, AsPC-1 showed NLRP3/ASC co-localization without detectable CASP1 mRNA expression or caspase-1 enzymatic activity, indicating incomplete inflammasome activation. CFPAC-1 displayed minimal expression of inflammasome-related genes, low caspase-1 activity, and weak cytokine output. ELISA confirmed that BxPC-3 secreted the highest levels of IL-1β, IL-6, and IL-8 proteins, correlating with elevated NFKB1 gene expression and pronounced caspase-8 enzyme activity, which may contribute to IL-1β maturation in the absence of canonical signalling.
These findings underscore the heterogeneity of inflammasome signalling across PDAC cell lines and suggest that AIM2 inflammasomes may drive a pro-inflammatory phenotype in BxPC-3. In contrast, AsPC-1 and CFPAC-1 may rely on alternative or suppressed inflammatory pathways. This insight may guide inflammation-targeted strategies for PDAC therapy.
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