title: Lipopolysaccharide and Curcumin Co-Stimulation Potentiates Olfactory Ensheathing Cell Phagocytosis Via Enhancing Their Activation.
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.
authors.affiliation: Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, China. haodingjun@126.com.|Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, 710054, China. haodingjun@126.com.
authors.forename: Ding-Jun
authors.initials: DJ
authors.lastname: Hao
authors.affiliation: Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, China.|Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, 710054, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Liu
authors.affiliation: Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, China.|Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, 710054, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, China.|Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, 710054, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, China.|Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, 710054, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, China.|Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, 710054, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, China.|Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, 710054, China.
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.affiliation: Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, China.|Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, 710054, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, Shaanxi, 710032, China.
authors.forename: Mingmei
authors.initials: M
authors.lastname: Wu
authors.affiliation: Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, China.|Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, 710054, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Loma Linda University Medical Center, Loma Linda, CA, 92354, USA.
authors.forename: Alfred
authors.initials: A
authors.lastname: Simental
authors.affiliation: Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, China. hebr888@163.com.|Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, 710054, China. hebr888@163.com.
authors.forename: Baorong
authors.initials: B
authors.lastname: He
authors.affiliation: Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, China. yanghao.71_99@yahoo.com.|Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Shaanxi, 710054, China. yanghao.71_99@yahoo.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D054360:Chemokine CXCL1 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology; D010587:Phagocytosis / Q000187:drug effects; D061251:Primary Cell Culture; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011956:Receptors, Cell Surface / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C408123:phosphatidylserine receptor; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D003474:Curcumin
keywords: Cell activation; Curcumin; Lipopolysaccharide; Neuron growth; Olfactory ensheathing cells; Phagocytosis