title: Interleukin-1β pre-treated bone marrow stromal cells alleviate neuropathic pain through CCL7-mediated inhibition of microglial activation in the spinal cord.
abstract: Although neuropathic pain is one of the most intractable diseases, recent studies indicate that systemic or local injection of bone marrow stromal cells (BMSCs) decreases pro-inflammatory cytokines release and alleviates neuropathic pain. However, it is still not clear whether pre-treated BMSCs have a strong anti-inflammatory and/or analgesia effect. Using the spinal nerve ligation model of neuropathic pain, IL-1β pre-treated BMSCs (IL-1β-BMSCs) were injected into rats followed by SNL in order to determine possible effects. Results indicated that IL-1β-BMSCs were more efficacious in both amelioration of neuropathic pain and inhibition of microglia activation. Specifically, microglia inhibition was found to be mediated by chemokine C-C motif ligand 7 (CCL7) but not CCL2. Results also showed that IL-1β-BMSCs had a stronger inhibitory effect on astrocyte activation as well as CCL7 release, which was found to be mediated by IL-10 not transforming growth factor-β1. In addition, we also found directional migration of IL-1β-BMSCs was mediated by inceased C-X-C motif chemokine ligand (CXCL) 13 expression following SNL. In conclusion, our results indicated IL-1β-BMSCs could inhibit microglia activation and neuropathic pain by decreasing CCL7 level in spinal cord.
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Trauma Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 650 Xin Songjiang Road, Shanghai, 201620, China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Deng
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
authors.forename: Haowei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, the Third People's Hospital of Yancheng, Yancheng, 224001, China.
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Interventional &Vascular Surgery, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D054410:Chemokine CCL7 / Q000378:metabolism*; D054382:Chemokine CXCL13 / Q000378:metabolism; D006930:Hyperalgesia / Q000150:complications / Q000473:pathology / Q000628:therapy; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D008026:Ligation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009437:Neuralgia / Q000150:complications / Q000473:pathology / Q000628:therapy*; D059225:Nociception / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology*; D013127:Spinal Nerves / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D054410:Chemokine CCL7; D054382:Chemokine CXCL13; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10