Fabp4 contributes toward regulating inflammatory gene expression and oxidative stress in Ctenopharyngodon idella
Fabp4 contributes toward regulating inflammatory gene expression and oxidative stress in Ctenopharyngodon idella
复制标题
DOI：
10.1016/j.cbpb.2022.110715
复制
发表时间：
2022-01-13
影响因子：
2.2
通讯作者：
Tian, Jing-jing
中科院分区：
文献类型：
--
作者：
Lei, Cai-xia;Xie, Yu-jing;Tian, Jing-jing
脂肪酸结合蛋白（Fabp）-4是FABP家族的成员。哺乳动物fabp 4已被证明参与炎症和免疫，而鱼类fabp 4的相关数据仍然有限。因此，我们进一步研究了fabp 4对草鱼免疫功能的影响。首次克隆了全长405 bp的fabp 4序列，与其他鱼类和哺乳动物的fabp 4序列具有高度同源性。Fabp 4在脂肪组织中的表达最高，其次是心脏、肌肉和肝脏。在体内，脂多糖（LPS）触发肾脏和脾脏中fabp 4、toll样受体（tlr）-22、白细胞介素（il）-1 β和肿瘤坏死因子（tnf）-α的表达。在离体条件下，暴露C. LPS诱导的Idella CIK细胞存活率降低，fabp 4表达增加。然而，FABP 4的抑制剂BMS 309403减轻了这些影响。此外，用LPS或fabp 4过表达质粒处理细胞导致活性氧（ROS）的产生和炎性基因表达的上调，包括tlr 22、I型干扰素（ifn-1）、干扰素调节因子（irf）-7、tnf α、il-1 β和干扰素β启动子刺激因子1。通过与BMS 309403预孵育改善这些效应。此外，与谷胱甘肽孵育细胞减少了ROS的产生和LPS和质粒处理引起的炎症基因的表达。这些结果表明，fabp 4通过升高ROS水平作为促炎分子发挥作用，为硬骨鱼类先天免疫的分子调控提供了新的理解。
Fatty acid-binding protein (Fabp)-4 is a member of the FABP family. Mammalian fabp4 has been demonstrated to involve in inflammation and immunity, whereas the related data of fish fabp4 remain limited. Therefore, we further investigated the effects of fabp4 on immunity in Ctenopharyngodon idella. The fabp4 sequence spanned 405 bp was cloned first, sharing high identity to fabp4 from other fish and mammals. Fabp4 expression was the highest in the adipose tissue, followed by the heart, muscle, and liver. In vivo, lipopolysaccharide (LPS) triggered the expression of fabp4, toll-like receptor (tlr)-22, interleukin (il)-1 beta, and tumor necrosis factor (tnf)-alpha in the kidney and spleen. In vitro, exposing C. idella CIK cells to LPS decreased their viability, and the expression of fabp4 was also increased by LPS. However, BMS309403, an inhibitor of FABP4, mitigated these effects. Furthermore, treating the cells with LPS or fabp4 overexpression plasmids resulted in reactive oxygen species (ROS) generation and upregulation of inflammatory genes expression, including tlr22, type-I interferon (ifn-1), interferon regulatory factor (irf)-7, tnf alpha, il-1 beta, and interferon-beta promoter stimulator 1. These effects were ameliorated by preincubation with BMS309403. Moreover, incubating the cells with glutathione reduced the production of ROS and the expression of inflammatory genes that were evoked by LPS and plasmid treatments. These results showed that fabp4 acts as a pro-inflammatory molecule via elevating ROS levels, providing a novel understanding of the molecular regulation of innate immunity in teleosts.