Bibliographic Details
| Title: |
Amlexanox attenuates LPS-induced neuroinflammatory responses in microglial cells via inhibition of NF–κB and STAT3 signaling pathways. |
| Authors: |
Phan Van, Thach1,2 (AUTHOR), Huyen Ton Nu Bao, Tien1 (AUTHOR), Leya, Mwense1 (AUTHOR), Zhou, Zixiong3 (AUTHOR), Jeong, Hyuneui1 (AUTHOR), Lim, Chae-Woong1 (AUTHOR), Kim, Bumseok1 (AUTHOR) bskims@jbnu.ac.kr |
| Source: |
Scientific Reports. 2/2/2024, Vol. 14 Issue 1, p1-16. 16p. |
| Abstract: |
Amlexanox is an anti-inflammatory and anti-allergic agent used clinically for the treatment of aphthous ulcers, allergic rhinitis, and asthma. Recent studies have demonstrated that amlexanox, a selective inhibitor of IkB kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1), suppresses a range of diseases or inflammatory conditions, such as obesity-related metabolic dysfunction and type 2 diabetes. However, the effects of amlexanox on neuroinflammatory responses to amlexanox have not yet been comprehensively studied. In this study, we investigated the novel therapeutic effect of amlexanox on LPS-induced neuroinflammation in vivo, and intraperitoneal injection of amlexanox markedly reduced LPS-induced IKKε levels, proinflammatory cytokines, and microglial activation, as evidenced by ionized calcium-binding adapter molecule 1 (Iba1) immunostaining. Furthermore, amlexanox significantly reduced proinflammatory cytokines and chemokines in LPS-induced bone marrow-derived macrophages (BMDM), murine BV2, and human HMC3 microglial cells. This data provided considerable evidence that amlexanox can be used as a preventive and curative therapy for neuroinflammatory and neurodegenerative diseases. In terms of mechanism aspects, our results demonstrated that the anti-inflammatory action of amlexanox in BV2 microglial cells was through the downregulation of NF-κB and STAT3 signaling pathways. In addition, the combination of amlexanox and SPI (a STAT3 selective inhibitor) showed high efficiency in inhibiting the production of neurotoxic and pro-inflammatory mediators. Overall, our data provide rational insights into the mechanisms of amlexanox as a potential therapeutic strategy for neuroinflammation-related diseases. [ABSTRACT FROM AUTHOR] |
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