Xu Qiushi, Jia Hongdou, Ma Li, Liu Guowen, Xu Chuang, Li Ying, Li Xinwei, Li Xiaobing
Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China.
BMC Vet Res. 2019 Feb 1;15(1):48. doi: 10.1186/s12917-019-1791-2.
Dairy cows with metabolic disorder in peripartal period display high inflammatory levels. Adipose tissue is a major endocrine organ, which is closely related to systemic inflammation. Retinoic acid (RA), an active metabolite of vitamin A, has shown potential therapeutic immunomodulatory properties. The objective of the study was to examine the effect of all-trans-RA (ATRA), the biologically most active metabolite of vitamin A, on lipopolysaccharide (LPS)-induced bovine adipocytes inflammatory responses and elucidate the underlying mechanisms. Primary cultured bovine adipocytes were treated with ATRA in the presence or absence of LPS. The treated cells were examined for the inflammatory responses and the activity of transforming growth factor beta 1 (TGFβ1) /Smad3 signaling pathway.
LPS treatment significantly decreased the expression levels of TGFβ1/Smad3 components and increased the content of pro-inflammatory cytokines. Treatment with ATRA could over-activate TGFβ1/Smad3 signaling pathway in bovine adipocytes and reversed the over-production of pro-inflammatory cytokines and inhibition of anti-inflammatory cytokines induced by LPS. Importantly, inhibition of TGFβ1/Smad3 signaling diminished the effects of ATRA on suppressing the proinflammatory responses induced by LPS. Furthermore, activation of TGFβ1/Smad3 signaling further extended the effects of ATRA on suppressing the proinflammatory responses on LPS stimulation.
In conclusion, ATRA stimulates TGFβ1/Smad3 signaling pathway and further suppresses bovine adipocytes inflammatory responses induced by LPS.
围产期患有代谢紊乱的奶牛表现出高炎症水平。脂肪组织是一个主要的内分泌器官，与全身炎症密切相关。视黄酸（RA）是维生素A的一种活性代谢产物，已显示出潜在的治疗性免疫调节特性。本研究的目的是检测维生素A生物活性最强的代谢产物全反式视黄酸（ATRA）对脂多糖（LPS）诱导的牛脂肪细胞炎症反应的影响，并阐明其潜在机制。在存在或不存在LPS的情况下，用ATRA处理原代培养的牛脂肪细胞。检测处理后细胞的炎症反应以及转化生长因子β1（TGFβ1）/Smad3信号通路的活性。
LPS处理显著降低了TGFβ1/Smad3组分的表达水平，并增加了促炎细胞因子的含量。用ATRA处理可过度激活牛脂肪细胞中的TGFβ1/Smad3信号通路，并逆转LPS诱导的促炎细胞因子的过量产生和抗炎细胞因子的抑制。重要的是，抑制TGFβ1/Smad3信号通路可减弱ATRA对抑制LPS诱导的促炎反应的作用。此外，激活TGFβ1/Smad3信号通路进一步增强了ATRA对LPS刺激下促炎反应的抑制作用。
总之，ATRA刺激TGFβ1/Smad3信号通路，并进一步抑制LPS诱导的牛脂肪细胞炎症反应。
