Role of TGF-β and p38 MAPK in TSG-6 Expression in Adipose Tissue-Derived Stem Cells In Vitro and In Vivo

被引:2
作者
Kwon, Hye Youn [1 ]
Yoon, Yongdae [2 ]
Hong, Ju-Eun [3 ]
Rhee, Ki-Jong [3 ]
Sohn, Joon Hyung [4 ]
Jung, Pil Young [1 ]
Kim, Moon Young [2 ,5 ]
Baik, Soon Koo [2 ,5 ]
Ryu, Hoon [1 ]
Eom, Young Woo [2 ]
机构
[1] Yonsei Univ, Dept Surg, Wonju Coll Med, Wonju 26426, South Korea
[2] Yonsei Univ, Regenerat Med Res Ctr, Wonju Coll Med, Wonju 26426, South Korea
[3] Yonsei Univ, Coll Software & Digital Healthcare Convergence, Dept Biomed Lab Sci, Mirae Campus, Wonju 26493, South Korea
[4] Yonsei Univ, Dept Convergence Med, Wonju Coll Med, Wonju 26426, South Korea
[5] Yonsei Univ, Dept Internal Med, Wonju Coll Med, Wonju 26426, South Korea
基金
新加坡国家研究基金会;
关键词
mesenchymal stem cells; TSG-6; TGF-beta; inflammation; macrophages; MESENCHYMAL STROMAL CELLS; UMBILICAL-CORD BLOOD; HUMAN BONE-MARROW; TNF-ALPHA; STEM/PROGENITOR CELLS; LUNG FIBROBLASTS; PROTEIN; MICE; ACTIVATION; EFFICACY;
D O I
10.3390/ijms25010477
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mesenchymal stem cells (MSCs) regulate immune cell activity by expressing tumor necrosis factor-alpha (TNF-alpha)-stimulated gene 6 (TSG-6) in inflammatory environments; however, whether anti-inflammatory responses affect TSG-6 expression in MSCs is not well understood. Therefore, we investigated whether transforming growth factor-beta (TGF-beta) regulates TSG-6 expression in adipose tissue-derived stem cells (ASCs) and whether effective immunosuppression can be achieved using ASCs and TGF-beta signaling inhibitor A83-01. TGF-beta significantly decreased TSG-6 expression in ASCs, but A83-01 and the p38 inhibitor SB202190 significantly increased it. However, in septic C57BL/6 mice, A83-01 further reduced the survival rate of the lipopolysaccharide (LPS)-treated group and ASC transplantation did not improve the severity induced by LPS. ASC transplantation alleviated the severity of sepsis induced by LPS+A83-01. In co-culture of macrophages and ASCs, A83-01 decreased TSG-6 expression whereas A83-01 and SB202190 reduced Cox-2 and IDO-2 expression in ASCs. These results suggest that TSG-6 expression in ASCs can be regulated by high concentrations of pro-inflammatory cytokines in vitro and in vivo, and that A83-01 and SB202190 can reduce the expression of immunomodulators in ASCs. Therefore, our data suggest that co-treatment of ASCs with TGF-beta or p38 inhibitors is not adequate to modulate inflammation.
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页数:15
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