Neurotherapeutics

, Volume 14, Issue 2, pp 502–518

Lipopolysaccharide and Curcumin Co-Stimulation Potentiates Olfactory Ensheathing Cell Phagocytosis Via Enhancing Their Activation

  • Ding-Jun Hao
  • Cuicui Liu
  • Lingling Zhang
  • Bo Chen
  • Qian Zhang
  • Rui Zhang
  • Jing An
  • Jingjing Zhao
  • Mingmei Wu
  • Yi Wang
  • Alfred Simental
  • Baorong He
  • Hao Yang
Original Article

DOI: 10.1007/s13311-016-0485-8

Cite this article as:
Hao, DJ., Liu, C., Zhang, L. et al. Neurotherapeutics (2017) 14: 502. doi:10.1007/s13311-016-0485-8

Abstract

The gradual deterioration following central nervous system (CNS) injuries or neurodegenerative disorders is usually accompanied by infiltration of degenerated and apoptotic neural tissue debris. A rapid and efficient clearance of these deteriorated cell products is of pivotal importance in creating a permissive environment for regeneration of those damaged neurons. Our recent report revealed that the phagocytic activity of olfactory ensheathing cells (OECs) can make a substantial contribution to neuronal growth in such a hostile environment. However, little is known about how to further increase the ability of OECs in phagocytosing deleterious products. Here, we used an in vitro model of primary cells to investigate the effects of lipopolysaccharide (LPS) and curcumin (CCM) co-stimulation on phagocytic activity of OECs and the possible underlying mechanisms. Our results showed that co-stimulation using LPS and CCM can significantly enhance the activation of OECs, displaying a remarkable up-regulation in chemokine (C-X-C motif) ligand 1, chemokine (C-X-C motif) ligand 2, tumor necrosis factor-α, and Toll-like receptor 4, increased OEC proliferative activity, and improved phagocytic capacity compared with normal and LPS- or CCM-treated OECs. More importantly, this potentiated phagocytosis activity greatly facilitated neuronal growth under hostile culture conditions. Moreover, the up-regulation of transglutaminase-2 and phosphatidylserine receptor in OECs activated by LPS and CCM co-stimulation are likely responsible for mechanisms underlying the observed cellular events, because cystamine (a specific inhibitor of transglutaminase-2) and neutrophil elastase (a cleavage enzyme of phosphatidylserine receptor) can effectively abrogate all the positive effects of OECs, including phagocytic capacity and promotive effects on neuronal growth. This study provides an alternative strategy for the repair of traumatic nerve injury and neurologic diseases with the application of OECs in combination with LPS and CCM.

Keywords

Olfactory ensheathing cells Cell activation Lipopolysaccharide Curcumin Phagocytosis Neuron growth 

Supplementary material

13311_2016_485_MOESM1_ESM.pdf (491 kb)
ESM 1(PDF 491 kb)
13311_2016_485_MOESM2_ESM.pdf (491 kb)
ESM 2(PDF 491 kb)
13311_2016_485_MOESM3_ESM.pdf (491 kb)
ESM 3(PDF 491 kb)

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2016

Authors and Affiliations

  • Ding-Jun Hao
    • 1
    • 2
  • Cuicui Liu
    • 1
    • 3
  • Lingling Zhang
    • 1
    • 3
  • Bo Chen
    • 1
    • 3
  • Qian Zhang
    • 1
    • 3
  • Rui Zhang
    • 1
    • 3
  • Jing An
    • 1
    • 3
  • Jingjing Zhao
    • 1
    • 3
  • Mingmei Wu
    • 4
  • Yi Wang
    • 1
    • 3
  • Alfred Simental
    • 5
  • Baorong He
    • 1
    • 2
  • Hao Yang
    • 1
    • 3
  1. 1.Shaanxi Spine Medicine Research Center, Hong Hui HospitalXi’an Jiaotong University College of MedicineShaanxiChina
  2. 2.Department of Spine Surgery, Hong Hui HospitalXi’an Jiaotong University College of MedicineShaanxiChina
  3. 3.Translational Medicine Center, Hong Hui HospitalXi’an Jiaotong University College of MedicineShaanxiChina
  4. 4.Institute of NeurosciencesThe Fourth Military Medical UniversityShaanxiChina
  5. 5.Department of Otolaryngology-Head and Neck SurgeryLoma Linda University Medical CenterLoma LindaUSA

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