2024-03-29T09:41:39Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00023340
2023-01-16T05:05:24Z
499:500:501
Minocycline selectively inhibits M1 polarization of microglia
Kobayashi, K
69176
Imagama, S
69177
Ohgomori, T
69178
Hirano, K
69179
Uchimura, K
69180
Sakamoto, K
69181
Hirakawa, A
69182
Takeuchi, H
69183
Suzumura, A
69184
Ishiguro, N
69185
Kadomatsu, K
69186
Minocycline is commonly used to inhibit microglial activation. It is widely accepted that activated microglia exert dual functions, that is, pro-inflammatory (M1) and anti-inflammatory (M2) functions. The in vivo status of activated microglia is probably on a continuum between these two extreme states. However, the mechanisms regulating microglial polarity remain elusive. Here, we addressed this question focusing on minocycline. We used SOD1G93A mice as a model, which exhibit the motor neuron-specific neurodegenerative disease, amyotrophic lateral sclerosis. Administration of minocycline attenuated the induction of the expression of M1 microglia markers during the progressive phase, whereas it did not affect the transient enhancement of expression of M2 microglia markers during the early pathogenesis phase. This selective inhibitory effect was confirmed using primary cultured microglia stimulated by lipopolysaccharide (LPS) or interleukin (IL)-4, which induced M1 or M2 polarization, respectively. Furthermore, minocycline inhibited the upregulation of NF-κB in the LPS-stimulated primary cultured microglia and in the spinal cord of SOD1G93A mice. On the other hand, IL-4 did not induce upregulation of NF-κB. This study indicates that minocycline selectively inhibits the microglia polarization to a proinflammatory state, and provides a basis for understanding pathogeneses of many diseases accompanied by microglial activation.
journal article
nature
2013-03-07
application/pdf
Cell Death and Disease
4
e525
e525
http://doi.org/10.1038/cddis.2013.54
http://hdl.handle.net/2237/25532
2041-4889
https://nagoya.repo.nii.ac.jp/record/23340/files/cddis201354a.pdf
eng
https://doi.org/10.1038/cddis.2013.54
Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/ licenses/by/3.0/