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The proinflammatory cytokine effects on neurotrophins production in bone marrow mesenchymal stem cells

Other Titles
 전염증성 싸이토카인이 중간엽줄기세포에서 뉴로트로핀 생성에 미치는 영향 
Authors
 정장균 
Issue Date
2011
Description
Dept. of Medicine/박사
Abstract
Understanding the mechanisms by which bone marrow stem cells produce neurotrophic factors may represent an important way to optimize their beneficial paracrine and autocrine effects. Components of the damaged nervous microenvironment may stimulate neurotrophic factor production to promote stem cell-mediated repair. We hypothesized that the proimflammatory cytokines (tumor necrosis factor-alpha or Interlukin1beta) may activate human bone marrow mesenchymal stem cells (BMSC) to increase the release of neurotrophic factors (nerve growth factor, brain derived nerve growth factor) and that nuclear factor-kappa B (NF kappa B), mitogen-activated protein kinases(MAPKs) pathway mediates neurotrophic factor production from human BMSC. Furthermore, to modify BMSC ex vivo to capitalize on the positive effects of cytokines, understanding of detail signal pathway is important. To study this, human BMSC were cultured, passaged, divided into four groups (100,000 cells, triplicates) and treated as follows: 1) with vehicle; 2) with stimulant alone (24 h TNF-alpha or 24 h IL-1β); 3) with inhibitor alone [NF kappa B (PDTC), p38MAPK(SB203580), or ERK (PD98059)]; and 4) with stimulant and the various inhibitors. After 24 h incubation, BMSC activation was determined by measuring expression for NGF, BDNF (RT-PCR, ELISA, Western blot). TNF-alpha but not IL-1β significantly increased human BMSC NGF production versus controls. Stem cells exposed to TNF-alpha demonstrated increased activation of NF kappa B, ERK, and p38MAPK. NGF expression was significantly reduced by NF kappa B and ERK inhibition but not p38MAPK inhibition. Inhibitor alone did not activate BMSC NGF expression over controls. Moreover, siRNA for RSK1 but not MSK1 could knock down NGF expression. With these results, TNF-alpha activates human BMSC to increase NGF expression, which depends on an NFkB and MEK/Erk/RSK pathway mechanism.
Files in This Item:
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Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 3. Dissertation
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/134100
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