ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1572604
This article is part of the Research TopicTargeted Drug Delivery and Mode of Action of Small Molecules in NeuroinflammationView all 5 articles
Erdafitinib diminishes LPS-mediated neuroinflammatory responses through NLRP3 in wild-type mice
Provisionally accepted
- Korea Brain Research Institute, Daegu, Republic of Korea
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Introduction: Erdafitinib is an FDA-approved inhibitor of fibroblast growth factor receptor (FGFR) that is used clinically to treat metastatic urothelial cancer. FGFR activation is involved in proinflammatory responses, but the potential effects of FGFR inhibitors like erdafitinib on neuroinflammatory responses in the brain have not been fully established. Methods: The effects of pretreatment with 1 or 5 μM erdafitinib on proinflammatory responses induced by 1 μg/ml or 200 ng/ml LPS in vitro were evaluated in BV2 microglial cells. For in vivo experiments, 3-month-old C57BL6/N mice were injected (i.p.) daily for 7 days with vehicle (5% DMSO + 40% PEG + 5% Tween80 + 50% saline) or 10 mg/kg erdafitinib. On the final day, the mice were injected (i.p.) with 10 mg/kg LPS or PBS after erdafitinib administration and sacrificed after 8 h. The mRNA and protein expression of neuroinflammatory-associated molecules were assessed in cells or mouse brain tissue by real-time PCR, immunofluorescence staining, and/or western blotting.Results and Discussion: In BV2 microglial cells, erdafitinib pretreatment significantly reduced the increases in proinflammatory cytokines, NLRP3 inflammasome activation and JNK/PLCsignaling induced by LPS. In C57BL6/N mice, erdafitinib pretreatment significantly suppressed LPS-stimulated microglial/astroglial activation and proinflammatory cytokine expression. Importantly, erdafitinib pretreatment significantly downregulated LPS-induced NLRP3 inflammasome activation and astroglial neuroinflammation-associated molecules in C57BL6/N mice. Collectively, our experiments demonstrate that erdafitinib pretreatment diminishes LPS-induced neuroinflammation by suppressing NLRP3 inflammasome activation in vitro and in vivo and suggest that erdafitinib is a potential therapeutic agent for neuroinflammation-related diseases.
Keywords: FGFR, Erdafitinib, Neuroinflammation, NLRP3, JNK
Received: 07 Feb 2025; Accepted: 25 Apr 2025.
Copyright: © 2025 Lee, Kim, Jung, Kim, Gu, Song and Hoe. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hyang-Sook Hoe, Korea Brain Research Institute, Daegu, Republic of Korea
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