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Inflammation Research
Published in: Inflammation Research 6/2023

14-06-2023 | Original Research Paper

Agmatine-IRF2BP2 interaction induces M2 phenotype of microglia by increasing IRF2-KLF4 signaling

Authors: Jiwon Kim, A Young Sim, Sumit Barua, Jong Youl Kim, Jong Eun Lee

Published in: Inflammation Research | Issue 6/2023

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Abstract

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.
Appendix
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Metadata
Title
Agmatine-IRF2BP2 interaction induces M2 phenotype of microglia by increasing IRF2-KLF4 signaling
Authors
Jiwon Kim
A Young Sim
Sumit Barua
Jong Youl Kim
Jong Eun Lee
Publication date
14-06-2023
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 6/2023
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-023-01741-z

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