دورية أكاديمية
Agmatine-IRF2BP2 interaction induces M2 phenotype of microglia by increasing IRF2-KLF4 signaling
| العنوان: | Agmatine-IRF2BP2 interaction induces M2 phenotype of microglia by increasing IRF2-KLF4 signaling |
|---|---|
| المساهمون: | Jiwon Kim, A Young Sim, Sumit Barua, Jong Youl Kim, Jong Eun Lee, Kim, Jong Youl |
| بيانات النشر: | Birkhäuser |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Agmatine* / metabolism, Agmatine* / pharmacology, Carrier Proteins / metabolism, DNA-Binding Proteins, Humans, Inflammation / metabolism, Interferon Regulatory Factor-2 / metabolism, Interferon Regulatory Factor-2 / pharmacology, Kruppel-Like Factor 4, Lipopolysaccharides / metabolism, Lipopolysaccharides / pharmacology, Microglia / metabolism, Neuroinflammatory Diseases, Phenotype, Transcription Factors / metabolism, Agmatine, IRF2, IRF2BP2, KLF4, Microglia, Neuroinflammation |
| الوصف: | Background: Following central nervous system (CNS) injury, the investigation for neuroinflammation is vital because of its pleiotropic role in both acute injury and long-term recovery. Agmatine (Agm) is well known for its neuroprotective effects and anti-neuroinflammatory properties. However, Agm's mechanism for neuroprotection is still unclear. We screened target proteins that bind to Agm using a protein microarray; the results showed that Agm strongly binds to interferon regulatory factor 2 binding protein (IRF2BP2), which partakes in the inflammatory response. Based on these prior data, we attempted to elucidate the mechanism by which the combination of Agm and IRF2BP2 induces a neuroprotective phenotype of microglia. Methods: To confirm the relationship between Agm and IRF2BP2 in neuroinflammation, we used microglia cell-line (BV2) and treated with lipopolysaccharide from Escherichia coli 0111:B4 (LPS; 20 ng/mL, 24 h) and interleukin (IL)-4 (20 ng/mL, 24 h). Although Agm bound to IRF2BP2, it failed to enhance IRF2BP2 expression in BV2. Therefore, we shifted our focus onto interferon regulatory factor 2 (IRF2), which is a transcription factor and interacts with IRF2BP2. Results: IRF2 was highly expressed in BV2 after LPS treatment but not after IL-4 treatment. When Agm bound to IRF2BP2 following Agm treatment, the free IRF2 translocated to the nucleus of BV2. The translocated IRF2 activated the transcription of Kruppel-like factor 4 (KLF4), causing KLF4 to be induced in BV2. The expression of KLF4 increased the CD206-positive cells in BV2. Conclusions: Taken together, unbound IRF2, resulting from the competitive binding of Agm to IRF2BP2, may provide neuroprotection against neuroinflammation via an anti-inflammatory mechanism of microglia involving the expression of KLF4. ; restriction |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1023-3830 1420-908X |
| العلاقة: | INFLAMMATION RESEARCH; J01059; OAK-2023-01936; OAK-2023-01937; https://ir.ymlib.yonsei.ac.kr/handle/22282913/195502Test; https://link.springer.com/article/10.1007/s00011-023-01741-zTest; T202303395; INFLAMMATION RESEARCH, Vol.72(6) : 1203-1213, 2023-06 |
| DOI: | 10.1007/s00011-023-01741-z |
| الإتاحة: | https://doi.org/10.1007/s00011-023-01741-zTest https://ir.ymlib.yonsei.ac.kr/handle/22282913/195502Test |
| حقوق: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.2A9E1CAC |
| قاعدة البيانات: | BASE |
| تدمد: | 10233830 1420908X |
|---|---|
| DOI: | 10.1007/s00011-023-01741-z |