title: Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving cannabinoid receptor CB2.
abstract: Chronic pain is commonly and closely correlated with inflammation. Both cannabinoid signaling and mesenchymal stem cells (MSCs) have been demonstrated to reduce inflammatory pain. Although cannabinoid signaling is essential for mesenchymal stem cell survival and differentiation, little is known about its role in modulatory effect of MSCs on inflammation and pain sensitivity. Here we showed that mouse bone-marrow derived MSCs (BM-MSCs) expressed both cannabinoid receptor type 1 and 2 (CB1 and CB2). CB2 expression level in BM-MSCs increased with their maturation. In addition, we found that tetrahydrocannabinol (THC) activated CB2 receptor and ERK signaling, consequently enhancing the modulation of MSCs on inflammation-associated cytokine release from lipopolysaccharides-stimulated microglia. Consistent with in vitro data, THC pretreatment enhanced the immunomodulatory effects of BM-MSC on thermal hyperalgesia and mechanical allodynia in chronic constriction injury model, by decreasing the release of pro-inflammation cytokines. Our study revealed the crucial role of THC in promoting the immunomodulatory effects of MSCs and proposed a new strategy to alleviate pain based on stem cells therapy.
authors.affiliation: Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Junran
authors.initials: J
authors.lastname: Xie
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, People's Republic of China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, People's Republic of China.
authors.forename: Dongju
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, People's Republic of China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Jinning
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, People's Republic of China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, People's Republic of China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Hu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, People's Republic of China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, People's Republic of China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Lina
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006930:Hyperalgesia / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D056747:Immunomodulation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D063386:Cannabinoid Receptor Agonists; D016207:Cytokines; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013759:Dronabinol
keywords: Immune response; Immunity; Immunology and Microbiology Section; cannabinoid receptor; inflammation; mesenchymal stem cells; pain; tetrahydrocannabinol
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