期刊
EXPERIMENTAL BIOLOGY AND MEDICINE
卷 240, 期 12, 页码 1622-1629出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1535370215584901
关键词
Ulcerative colitis; bifidobacteria; interleukin 10; T helper 17 cells; regulatory T cells
资金
- Science and Technology Planning Project of Shenzhen [201201013, 201302015]
- Technical Research and Development Project of Shenzhen [JCYJ20130402092657774]
- Jinan University of Medical Sciences, Shenzhen People's Hospital
Ulcerative colitis (UC) is a chronic inflammatory bowel disease suggested to be closely related to the imbalance of regulatory T cell/T helper 17 cell (Treg/Th17) signaling. Previously, we constructed an interleukin-10 (IL-10) expression vector, BL-hIL-10, and proved that it ameliorates dextran sulfate sodium-induced intestinal inflammation in mice. In this study, we further explored the mechanisms underlying BL-hIL-10 treatment from the Treg/Th17 imbalance perspective. Our results showed that the oral administration of BL-hIL-10 reduced the UC inflammation in mice significantly, which was assessed by disease activity index, spleen index, and pathological changes in colon tissue. Moreover, the mice after BL-hIL-10 treatment had increased proportion of Treg cells while Th17 cells decreased greatly, leading to the reconstruction of Treg/Th17 balance. Furthermore, the Th17 cell-secreted factors, such as IL-6, IL-17, and IL-23, were reduced, but the Treg-related factors, IL-10 and Transforming growth factor-beta 1 (TGF-beta 1), were elevated accordingly. Finally, Western blot confirmed the inhibition of nuclear hypoxia-inducible factor-1 alpha (HIF-1 alpha) and cytoplasmic mechanistic target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) in intestinal tissues. In conclusion, oral administration of BL-hIL-10 can alleviate the inflammation responses of UC in murine model through the restoration of Treg/Th17 imbalance, which might be at least partially due to the inhibition of hypoxia-mTOR-HIF-1 alpha-Th17 axis as well as IL-6-STAT3-HIF-1 alpha-Th17 pathway.
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