PMID- 19269277
OWN - NLM
STAT- MEDLINE
DCOM- 20090729
LR  - 20131121
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1269
DP  - 2009 May 7
TI  - Effects of human marrow stromal cells on activation of microglial cells and 
      production of inflammatory factors induced by lipopolysaccharide.
PG  - 23-30
LID - 10.1016/j.brainres.2009.02.049 [doi]
AB  - 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.
FAU - Zhou, Chang
AU  - Zhou C
AD  - Department of Neurology, The Affiliated Hospital of Medical College Qingdao 
      University, 16 Jiangsu Road, Qingdao, Shandong, 266003, PR China.
FAU - Zhang, Chen
AU  - Zhang C
FAU - Chi, Song
AU  - Chi S
FAU - Xu, Yiongfeng
AU  - Xu Y
FAU - Teng, Jijun
AU  - Teng J
FAU - Wang, Haiping
AU  - Wang H
FAU - Song, Yuqiang
AU  - Song Y
FAU - Zhao, Renliang
AU  - Zhao R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090306
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*cytology
MH  - Cell Communication/drug effects/*immunology
MH  - Cell Survival/immunology
MH  - Cells, Cultured
MH  - Culture Media, Conditioned/pharmacology
MH  - Down-Regulation/immunology
MH  - Humans
MH  - Inflammation/chemically induced/*immunology
MH  - Lipopolysaccharides/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/*cytology/metabolism
MH  - Nerve Growth Factors/metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase/metabolism
MH  - Phosphorylation
MH  - Stromal Cells/*cytology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2009/03/10 09:00
MHDA- 2009/07/30 09:00
CRDT- 2009/03/10 09:00
PHST- 2008/08/22 00:00 [received]
PHST- 2009/02/01 00:00 [revised]
PHST- 2009/02/22 00:00 [accepted]
PHST- 2009/03/10 09:00 [entrez]
PHST- 2009/03/10 09:00 [pubmed]
PHST- 2009/07/30 09:00 [medline]
AID - S0006-8993(09)00419-3 [pii]
AID - 10.1016/j.brainres.2009.02.049 [doi]
PST - ppublish
SO  - Brain Res. 2009 May 7;1269:23-30. doi: 10.1016/j.brainres.2009.02.049. Epub 2009 
      Mar 6.