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bioRxiv · 10.64898/2025.12.30.697027

NLRP3 Inflammasome Exhibits Context-Dependent Roles in Glioblastoma-Astrocyte Crosstalk

Rajkhowa, S.·Sha, L.·Meena, D.·Kumar, D.·Revanth, M.·Janu, V.·Garg, M.·Agrawal, M.·Jha, D.·Jha, S.
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Abstract

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by molecular and cellular heterogeneity and poor patient survival. NLRP3 inflammasome regulates inflammation and cell death with context-specific roles in cancer, but its functions in GBM tumour and astrocyte interactions remain unclear. In this study, we analyzed NLRP3 expression and function in GBM cell lines (LN-229 and LN18), astrocytes (SVG), patient-derived tissues, and organoids. Basal NLRP3 expression was higher in astrocytes than in GBM cells and increased after LPS stimulation, altering astrocyte morphology and NLRP3 subcellular localization. siRNA-mediated silencing of NLRP3 reduced GBM proliferation, migration, and viability in GBM cells, while enhancing proliferation and cytokine secretion in astrocytes, highlighting its context-dependent effects. NLRP3 deficiency exhibited reciprocal cytokine paracrine signaling, with GBM cells releasing elevated levels of IL-6 and TNF-, and astrocytes releasing elevated levels of IL-1{beta}. Glyburide treatment reduced NLRP3 expression and IL-1{beta} release in GBM cells but elevated NLRP3 and IL-1{beta} in astrocytes. Overall, these data reveal NLRP3s dual roles in GBM-astrocyte crosstalk, suggesting cell-type-selective inhibition for therapeutic exploration.

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Rajkhowa, S., Sha, L., Meena, D., Kumar, D., Revanth, M., Janu, V., Garg, M., Agrawal, M., Jha, D., Jha, S.. 2025-12-30. NLRP3 Inflammasome Exhibits Context-Dependent Roles in Glioblastoma-Astrocyte Crosstalk. https://doi.org/10.64898/2025.12.30.697027

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