Jiang Jun, Shi Dan, Zhou Xiao-Qiu, Yin Long, Feng Lin, Jiang Wei-Dan, Liu Yang, Tang Ling, Wu Pei, Zhao Ye
1Department of Aquaculture,College of Animal Science and Technology,Sichuan Agricultural University,Chengdu 611130,People's Republic of China.
2Animal Nutrition Institute,Sichuan Agricultural University,Chengdu 611130,People's Republic of China.
Br J Nutr. 2015 Nov 28;114(10):1560-8. doi: 10.1017/S0007114515003256. Epub 2015 Sep 8.
The present study was conducted to investigate the anti-inflammatory effect of vitamin D both in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. In primary enterocytes, exposure to 10 mg lipopolysaccharide (LPS)/l increased lactate dehydrogenase activity in the culture medium (P<0·05) and resulted in a significant loss of cell viability (P<0·05). LPS exposure increased (P<0·05) the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), which was decreased by pre-treatment with 1,25-dihydroxyvitamin D (1,25D3) in a dose-dependent manner (P<0·05). Further results showed that pre-treatment with 1,25D3 down-regulated Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88) and NF-κB p65 mRNA expression (P<0·05), suggesting potential mechanisms against LPS-induced inflammatory response. In vivo, intraperitoneal injection of LPS significantly increased TNF-α, IL-1β, IL-6 and IL-8 mRNA expression in the intestine of carp (P<0·05). Pre-treatment of fish with vitamin D3 protected the fish intestine from the LPS-induced increase of TNF-α, IL-1β, IL-6 and IL-8 mainly by downregulating TLR4, Myd88 and NF-κB p65 mRNA expression (P<0·05). These observations suggest that vitamin D could inhibit LPS-induced inflammatory response in juvenile Jian carp in vivo and in enterocytes in vitro. The anti-inflammatory effect of vitamin D is mediated at least in part by TLR4-Myd88 signalling pathways in the intestine and enterocytes of juvenile Jian carp.
本研究旨在探讨维生素D对建鲤幼鱼体内及体外肠细胞的抗炎作用。在原代肠细胞中,暴露于10 mg脂多糖(LPS)/l会增加培养基中的乳酸脱氢酶活性(P<0·05),并导致细胞活力显著丧失(P<0·05)。LPS暴露会增加(P<0·05)促炎细胞因子(TNF-α、IL-1β、IL-6和IL-8)的mRNA表达,而1,25-二羟基维生素D(1,25D3)预处理可使其呈剂量依赖性降低(P<0·05)。进一步结果表明,1,25D3预处理可下调Toll样受体4(TLR4)、髓样分化初级反应基因88(Myd88)和NF-κB p65的mRNA表达(P<0·05),提示其可能是对抗LPS诱导的炎症反应的潜在机制。在体内,腹腔注射LPS可显著增加鲤鱼肠道中TNF-α、IL-1β、IL-6和IL-8的mRNA表达(P<0·05)。用维生素D3预处理鱼类可保护鱼肠道免受LPS诱导的TNF-α、IL-1β、IL-6和IL-8增加的影响,主要是通过下调TLR4、Myd88和NF-κB p65的mRNA表达(P<0·05)。这些观察结果表明,维生素D可抑制建鲤幼鱼体内及体外肠细胞中LPS诱导的炎症反应。维生素D的抗炎作用至少部分是通过建鲤幼鱼肠道和肠细胞中的TLR4-Myd88信号通路介导的。