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Enhanced Anti-inflammatory Effects of TNF-α and IFN-γ Treated Canine Mesenchymal Stem Cells Through the COX-2/PGE2 Pathway : TNF-α 및 IFN-γ로 처리된 개 중간엽줄기세포의 COX-2/PGE2 경로를 통한 항염증 효과 향상
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- Authors
- Advisor
- 윤화영
- Major
- 수의과대학 수의학과
- Issue Date
- 2018-02
- Publisher
- 서울대학교 대학원
- Keywords
- mesenchymal stem cell ; inflammatory cytokines ; COX-2 ; PGE2 ; anti-inflammation
- Description
- 학위논문 (석사)-- 서울대학교 대학원 : 수의과대학 수의학과, 2018. 2. 윤화영.
- Abstract
- Mesenchymal stem cells (MSCs) have been used in studies on treatment of various diseases, and their application to immune-mediated diseases has garnered interest. Various methods for enhancing the immunomodulation effect of human MSCs have been used
however, similar approaches for canine MSCs are relatively unexplored. Accordingly, I evaluated immunomodulatory effects and mechanisms in canine MSCs treated with TNF-α and IFN-γ. Canine MSCs were stimulated with TNF-α and IFN-γ for 24 hours to produce conditioned media (CM). Lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were co-cultured with the MSCs for 48 h in CM. Expression of RNA was assessed by quantitative reverse transcription PCR (qRT-PCR), and protein levels were assessed by western blot. Expression of inducible nitric oxide synthase (iNOS), IL-6 and IL-1β was significantly (one-way ANOVA) decreased in LPS-stimulated RAW 264.7 cells co-cultured with naïve canine MSCs compared to that in LPS-stimulated RAW 264.7 cells alone. Furthermore, anti-inflammatory effects of TNF-α- and IFN-γ-primed canine MSCs were significantly increased compared with those of naïve canine MSCs. Expression of cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) were likewise significantly increased in primed canine MSCs. The level of iNOS protein in LPS-stimulated RAW 264.7 cells co-cultured with the primed canine MSCs was decreased, but it increased when the cells were treated with NS-398(PGE2 inhibitor). In conclusion, compared with naïve canine MSCs, cells primed with TNF-α and IFN-γ cause a greater reduction in release of anti-inflammatory cytokines from LPS-stimulated RAW 264.7 cells
the mechanism is upregulation of the COX-2/PGE2 pathway.
- Language
- English
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