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- Title
Role of TGF-β and p38 MAPK in TSG-6 Expression in Adipose Tissue-Derived Stem Cells In Vitro and In Vivo.
- Authors
Kwon, Hye Youn; Yoon, Yongdae; Hong, Ju-Eun; Rhee, Ki-Jong; Sohn, Joon Hyung; Jung, Pil Young; Kim, Moon Young; Baik, Soon Koo; Ryu, Hoon; Eom, Young Woo
- Abstract
Mesenchymal stem cells (MSCs) regulate immune cell activity by expressing tumor necrosis factor-α (TNF-α)-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-β (TGF-β) regulates TSG-6 expression in adipose tissue-derived stem cells (ASCs) and whether effective immunosuppression can be achieved using ASCs and TGF-β signaling inhibitor A83-01. TGF-β 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-β or p38 inhibitors is not adequate to modulate inflammation.
- Subjects
GENE expression; STEM cells; MESENCHYMAL stem cells; TRANSFORMING growth factors; MITOGEN-activated protein kinases; LABORATORY mice
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 1, p477
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25010477