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

Elsevier BV - Tập 14 - Trang 502-518 - 2016
Ding-Jun Hao1,2, Cuicui Liu1,3, Lingling Zhang1,3, Bo Chen1,3, Qian Zhang1,3, Rui Zhang1,3, Jing An1,3, Jingjing Zhao1,3, Mingmei Wu4, Yi Wang1,3, Alfred Simental5, Baorong He1,2, Hao Yang1,3
1Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Shaanxi, China
2Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Shaanxi, China
3Translational Medicine Center, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Shaanxi, China
4Institute of Neurosciences, The Fourth Military Medical University, Shaanxi, China
5Department of Otolaryngology-Head and Neck Surgery, Loma Linda University Medical Center, Loma Linda, USA

Tóm tắt

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.

Tài liệu tham khảo

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