Minocycline selectively inhibits M1 polarization of microglia

K. Kobayashi, S. Imagama, Tomohiro Ohgomori, K. Hirano, K. Uchimura, K. Sakamoto, A. Hirakawa, H. Takeuchi, A. Suzumura, N. Ishiguro, K. Kadomatsu

Research output: Contribution to journalArticle

270 Citations (Scopus)

Abstract

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-kB 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-kB. 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.

Original languageEnglish
JournalCell Death and Disease
Volume4
Issue number3
DOIs
Publication statusPublished - Mar 1 2013
Externally publishedYes

Fingerprint

Minocycline
Microglia
NF-kappa B
Interleukin-4
Lipopolysaccharides
Up-Regulation
Amyotrophic Lateral Sclerosis
Motor Neurons
Neurodegenerative Diseases
Spinal Cord
Anti-Inflammatory Agents

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Kobayashi, K., Imagama, S., Ohgomori, T., Hirano, K., Uchimura, K., Sakamoto, K., ... Kadomatsu, K. (2013). Minocycline selectively inhibits M1 polarization of microglia. Cell Death and Disease, 4(3). https://doi.org/10.1038/cddis.2013.54

Minocycline selectively inhibits M1 polarization of microglia. / Kobayashi, K.; Imagama, S.; Ohgomori, Tomohiro; Hirano, K.; Uchimura, K.; Sakamoto, K.; Hirakawa, A.; Takeuchi, H.; Suzumura, A.; Ishiguro, N.; Kadomatsu, K.

In: Cell Death and Disease, Vol. 4, No. 3, 01.03.2013.

Research output: Contribution to journalArticle

Kobayashi, K, Imagama, S, Ohgomori, T, Hirano, K, Uchimura, K, Sakamoto, K, Hirakawa, A, Takeuchi, H, Suzumura, A, Ishiguro, N & Kadomatsu, K 2013, 'Minocycline selectively inhibits M1 polarization of microglia', Cell Death and Disease, vol. 4, no. 3. https://doi.org/10.1038/cddis.2013.54
Kobayashi, K. ; Imagama, S. ; Ohgomori, Tomohiro ; Hirano, K. ; Uchimura, K. ; Sakamoto, K. ; Hirakawa, A. ; Takeuchi, H. ; Suzumura, A. ; Ishiguro, N. ; Kadomatsu, K. / Minocycline selectively inhibits M1 polarization of microglia. In: Cell Death and Disease. 2013 ; Vol. 4, No. 3.
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