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Effect of Butyrates on Intestinal Epithelial Cells, Macrophages and Experimental Colitis In Mice : 장상피세포, 대식세포 및 대장염에서 부틸레이트의 효과
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- Authors
- Advisor
- 김병관
- Major
- 의과대학 임상의과학과
- Issue Date
- 2018-08
- Publisher
- 서울대학교 대학원
- Description
- 학위논문 (박사)-- 서울대학교 대학원 : 의과대학 임상의과학과, 2018. 8. 김병관.
- Abstract
- Introduction: Butyrate is a bacterial metabolite of dietary fiber in the colon that has been used to treat inflammatory disease. However, the effect of oral supplementation with butyrate on colitis has not been fully explored. We evaluated the effects of and mechanisms underlying oral supplementation with butyrate on experimental murine colitis.
Methods: The human intestinal epithelial cells (IECs) COLO 205, the murine macrophages RAW 264.7 and peritoneal macrophage from IL-10 deficient (IL-10-/-) mice were used. The production of cytokines was determined by ELISA. The effect of sodium butyrate on LPS-induced NF-κB pathway and acetylation of histone H3 were examined by Western blot analysis. The DNA binding activity of NF-κB was assessed by an electrophoretic mobility shift assay. To confirm that butyrate plays a protective role in colitis, an acute colitis model induced by dextran sulfate sodium (DSS) and a chronic colitis model in IL-10-/- mice were used. Colitis was quantified by histologic evaluation and immunohistochemcal staining was performed.
Results: Butyrate (100 μM and 500 μM) inhibited pro-inflammatory cytokine production (i.e., IL-8 in COLO205 and TNF-α, IL-6 and IL-12 in macrophages) but promoted anti-inflammatory cytokine (i.e., IL-10) production in RAW 264.7 cells. Butyrate attenuated both the LPS-induced degradation /phosphorylation of IκBα and DNA binding of NF-κB and enhanced histone H3 acetylation. The administration of oral butyrate (100 mg/kg) significantly improved histological scores in both colitis models, including the IL-10-/- mice. In immunohistochemical staining, IκBα phosphorylation was attenuated, and histone H3 acetylation was reversed in the treated colons of both colitis models.
Conclusions: Our results indicate that oral supplementation with butyrate attenuates experimental murine colitis by blocking NF- κB signaling and reverses histone acetylation. These anti-colitic effects of butyrate were IL-10 independent. Butyrate could be a candidate for a therapeutic agent for colitis.
- Language
- English
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