title: Effects of human marrow stromal cells on activation of microglial cells and production of inflammatory factors induced by lipopolysaccharide.
abstract: There has been an increasing appreciation of the role that microglial cells play in neural damage. Marrow stromal cells (MSCs) can dramatically lessen neural damage in animal models, but the mechanisms involved have not been defined. This study aimed to investigate the effects of human MSCs (hMSCs) on the activation of primary microglia and the attendant production of pro-inflammatory factors stimulated by bacterial endotoxin lipopolysaccharide (LPS). Our study showed that hMSCs in co-cultures and in transwell cultures inhibited the activation of microglial cells, reduced the production of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO), downregulated the expression of inducible nitric oxide synthase (iNOS) and phosphorylated p38 mitogen-activated protein kinase (p38 MAPK), whereas hMSCs conditioned medium did not have any effect on microglial inflammation. To further investigate the mechanisms by which hMSCs exert anti-inflammatory effects, we examined the production of neurotrophic factors by hMSCs with enzyme linked immunosorbent assay (ELISA). Our results showed that the production of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and hepatocyte growth factor (HGF) was significantly increased by hMSCs when cultured in the conditioned medium from activated microglia. We conclude that hMSCs can inhibit microglial activation and the production of attendant inflammatory factors. In addition, hMSCs can interact with microglial cells through diffusible soluble factors, whereas cell contact is not a prerequisite for anti-inflammatory effects. Finally, hMSCs within inflammatory environment can significantly increase the production of neurotrophic factors, which may involve with the anti-inflammatory mechanisms.
authors.affiliation: Department of Neurology, The Affiliated Hospital of Medical College Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, 266003, PR China.
authors.forename: Chang
authors.initials: C
authors.lastname: Zhou
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: Chi
authors.forename: Yiongfeng
authors.initials: Y
authors.lastname: Xu
authors.forename: Jijun
authors.initials: J
authors.lastname: Teng
authors.forename: Haiping
authors.initials: H
authors.lastname: Wang
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Song
authors.forename: Renliang
authors.initials: R
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010766:Phosphorylation; D017154:Stromal Cells / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D048051:p38 Mitogen-Activated Protein Kinases