Low-level laser therapy 810-nm up-regulates macrophage secretion of neurotrophic factors via PKA-CREB and promotes neuronal axon regeneration in vitro

J Cell Mol Med. 2020 Jan;24(1):476-487. doi: 10.1111/jcmm.14756. Epub 2019 Oct 31.


Macrophages play key roles in the secondary injury stage of spinal cord injury (SCI). M1 macrophages occupy the lesion area and secrete high levels of inflammatory factors that hinder lesion repair, and M2 macrophages can secrete neurotrophic factors and promote axonal regeneration. The regulation of macrophage secretion after SCI is critical for injury repair. Low-level laser therapy (810-nm) (LLLT) can boost functional rehabilitation in rats after SCI; however, the mechanisms remain unclear. To explore this issue, we established an in vitro model of low-level laser irradiation of M1 macrophages, and the effects of LLLT on M1 macrophage polarization and neurotrophic factor secretion and the related mechanisms were investigated. The results showed that LLLT irradiation decreased the expression of M1 macrophage-specific markers, and increased the expression of M2 macrophage-specific markers. Through forward and reverse experiments, we verified that LLLT can promote the secretion of various neurotrophic factors by activating the PKA-CREB pathway in macrophages and finally promote the regeneration of axons. Accordingly, LLLT may be an effective therapeutic approach for SCI with clinical application prospects.

Keywords: M1 macrophage; axonal regeneration; low-level laser therapy; macrophage polarization; spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / metabolism*
  • Axons / radiation effects
  • Culture Media, Conditioned / pharmacology
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Female
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Isoquinolines / pharmacology
  • Low-Level Light Therapy*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Macrophages / radiation effects*
  • Male
  • Mice, Inbred BALB C
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Nerve Regeneration* / drug effects
  • Nerve Regeneration* / radiation effects
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sulfonamides / pharmacology


  • Culture Media, Conditioned
  • Cyclic AMP Response Element-Binding Protein
  • Isoquinolines
  • Nerve Growth Factors
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Sulfonamides
  • Cyclic AMP-Dependent Protein Kinases
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide