Suppression of LPS-Induced Inflammation and Cell Migration by Azelastine through Inhibition of JNK/NF-κB Pathway in BV2 Microglial Cells
| Autor: | Bich Phuong Bui, Men Thi Hoai Duong, Kyeong Lee, Hee-Chul Ahn, Jungsook Cho, Phuong Linh Nguyen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide Anti-Inflammatory Agents Nitric Oxide Synthase Type II Pharmacology neuroinflammation chemistry.chemical_compound Mice Cell Movement Biology (General) Spectroscopy c-Jun N-terminal kinase drug repurposing Kinase NF-kappa B Cell migration General Medicine Computer Science Applications Chemistry Phosphorylation Tumor necrosis factor alpha Microglia medicine.symptom Inflammation Mediators Signal Transduction JNK inhibitor structure-based virtual screening QH301-705.5 MAP Kinase Signaling System Inflammation BV2 microglial cells Nitric Oxide Catalysis Article Cell Line Inorganic Chemistry medicine Animals nuclear factor-kappa B (NF-κB) Physical and Theoretical Chemistry Molecular Biology QD1-999 Neuroinflammation Interleukin-6 Tumor Necrosis Factor-alpha Organic Chemistry JNK Mitogen-Activated Protein Kinases NF-κB chemistry azelastine Phthalazines |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 9061, p 9061 (2021) Volume 22 Issue 16 |
| ISSN: | 1422-0067 |
| Popis: | The c-Jun N-terminal kinases (JNKs) are implicated in many neuropathological conditions, including neurodegenerative diseases. To explore potential JNK3 inhibitors from the U.S. Food and Drug Administration-approved drug library, we performed structure-based virtual screening and identified azelastine (Aze) as one of the candidates. NMR spectroscopy indicated its direct binding to the ATP-binding site of JNK3, validating our observations. Although the antihistamine effect of Aze is well documented, the involvement of the JNK pathway in its action remains to be elucidated. This study investigated the effects of Aze on lipopolysaccharide (LPS)-induced JNK phosphorylation, pro-inflammatory mediators, and cell migration in BV2 microglial cells. Aze was found to inhibit the LPS-induced phosphorylation of JNK and c-Jun. It also inhibited the LPS-induced production of pro-inflammatory mediators, including interleukin-6, tumor necrosis factor-α, and nitric oxide. Wound healing and transwell migration assays indicated that Aze attenuated LPS-induced BV2 cell migration. Furthermore, Aze inhibited LPS-induced IκB phosphorylation, thereby suppressing nuclear translocation of NF-κB. Collectively, our data demonstrate that Aze exerts anti-inflammatory and anti-migratory effects through inhibition of the JNK/NF-κB pathway in BV2 cells. Based on our findings, Aze may be a potential candidate for drug repurposing to mitigate neuroinflammation in various neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. |
| Databáze: | OpenAIRE |
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