Keewan Esra'a, Narasimhulu Chandrakala Aluganti, Rohr Michael, Hamid Simran, Parthasarathy Sampath
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
Antioxidants (Basel). 2020 Sep 27;9(10):926. doi: 10.3390/antiox9100926.
Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder characterized by progressive inflammation and the erosion of the gut mucosa. Although the exact cause of IBD is unknown, multiple factors contribute to its complex pathogenesis. Diet is one such factor and a strong correlation exists between the western-style, high fat diets (HFDs) and IBD incidence rates. In this study, we propose that the peroxidized fatty acid components of HFDs could contribute to inflammation of the gut. The inflammatory nature of peroxidized linoleic acid (13-HPODE), was confirmed in vitro by analyzing pro-inflammatory gene expression in Caco-2 cells via RT-PCR and ELISA. Additionally, peroxide induced apoptosis was tested by Annexin-V fluorescent staining, while permeability was tested by FITC-dextran flux and TEER. The 13-HPODE-induced inflammation of intestinal epithelium was evaluated in vivo by analyzing pro-inflammatory cytokines under acute and chronic conditions after feeding 13-HPODE to C57BL/6J mice. Our data show that 13-HPODE significantly induced pro-inflammatory gene expression of TNF-α and MCP-1 in vitro, most notably in differentiated Caco-2 cells. Further, acute and chronic 13-HPODE treatments of mice similarly induced pro-inflammatory cytokine expression in the epithelium of both the proximal and distal small intestines, resident immune cells in Peyer's patches and peritoneal macrophages. The results of this study not only confirm the pro-inflammatory properties of peroxidized fats on the gut mucosa, but for the first time demonstrate their ability to differentially induce pro-inflammatory gene expression and influence permeability in the intestinal epithelium and mucosal cells. Collectively, our results suggest that the immunogenic properties of HFD's in the gut may be partly caused by peroxide derivatives, providing potential insight into how these diets contribute to exacerbations of IBD.
炎症性肠病（IBD）是一种慢性炎症性疾病，其特征是肠道黏膜进行性炎症和糜烂。尽管IBD的确切病因尚不清楚，但多种因素导致了其复杂的发病机制。饮食就是其中一个因素，西式高脂肪饮食（HFDs）与IBD发病率之间存在密切关联。在本研究中，我们提出HFDs中的过氧化脂肪酸成分可能导致肠道炎症。通过RT-PCR和ELISA分析Caco-2细胞中的促炎基因表达，在体外证实了过氧化亚油酸（13-HPODE）的炎症性质。此外，通过膜联蛋白-V荧光染色检测过氧化物诱导的细胞凋亡，同时通过FITC-葡聚糖通量和跨上皮电阻检测通透性。在给C57BL/6J小鼠喂食13-HPODE后，通过分析急性和慢性条件下的促炎细胞因子，在体内评估13-HPODE诱导的肠上皮炎症。我们的数据表明，13-HPODE在体外显著诱导TNF-α和MCP-1的促炎基因表达，最显著的是在分化的Caco-2细胞中。此外，对小鼠进行急性和慢性13-HPODE处理同样诱导近端和远端小肠上皮、派尔集合淋巴结中的驻留免疫细胞和腹腔巨噬细胞中的促炎细胞因子表达。本研究结果不仅证实了过氧化脂肪对肠道黏膜的促炎特性，而且首次证明了它们有能力差异性地诱导促炎基因表达并影响肠上皮和黏膜细胞的通透性。总的来说，我们的结果表明HFDs在肠道中的免疫原性特性可能部分由过氧化物衍生物引起，这为这些饮食如何导致IBD病情加重提供了潜在的见解。
