Minocycline selectively inhibits M1 polarization of microglia

By Kazuyoshi Kobayashi, S. Imagama, Tomohiro Ohgomori, K. Hirano, K. Uchimura, Kazuma Sakamoto, Akihiro Hirakawa, H. Takeuchi, A. Suzumura, N. Ishiguro and 1 more. Cell Death and Disease, 2013

699 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/dd2d34d5c49499cebaeb5e5cf56d2451acf74dad

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In Cellular and Molecular Neuroscience

1. Yuanyuan Tang
2. Christoph Weder
3. Mehdi Jorfi
4. W. Le
5. John Skousen
6. Jeffrey R. Capadona

In Neurology

1. Guo-Yuan Yang
2. Liang Liu
3. Yuanyuan Tang
4. Yongting Wang
5. Qing-Wu Yang
6. Xiao-Yi Xiong
7. Jixian Wang
8. Yuanyuan Ma

Citations in the corpus

• Progress Towards Biocompatible Intracortical Microelectrodes for Neural Interfacing Applications (2014, methodology): “The drug used in Rennekar’s study, Minocycline, is a tetracycline antibiotic known to shift macrophages and microglia away from a pro-inflammatory (M1) phenotype [180, 181].”
• The biphasic function of microglia in ischemic stroke (2017, positive): “Minocycline was also shown to modulate microglia polarization during the early pathogenesis phase of amyotrophic lateral sclerosis (ALS), in which microglia are significantly activated (Kobayashi et al., 2013; Liao et al., 2012).”
• Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke. (2016, methodology): “Accordingly, minocycline, a selective inhibitor of microglial M1 polarization that does not affect the expression of M2 microglia markers (Kobayashi et al., 2013), was used for chronic treatment and was found to promote neurogenesis and functional recovery after focal cerebral ischemia (Liu et al.,…”
• Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases (2015, background): “The chemicals as fasudil [84] and minocycline [141], which have the superior ability to cross the”