Akademik Veri Yönetim Sistemi
World Immune Regulation Meeting XVIII 2024, Chur, İsviçre, 13 - 16 Mart 2024, cilt.18, sa.14, ss.39
The barrier function of the epithelia is crucial for maintaining homeostasis. Environmental exposures may alter the epithelial barrier integrity and influence the development of diseases. Recent studies have shown that certain surfactants and emulsifiers damage the epithelial barriers. In the present study, we are aiming to show the effects of three commonly used food emulsifiers, sunflower-derived lecithin (SunLec), soy lecithin (SoyLec) and diacetyl tartaric acid ester of mono- and diglycerides (DATEM) on gut-on-a-chip. All emulsifiers were examined at consumer-relevant doses using transepithelial electrical resistance (TEER), RNA-seq, and targeted proteomics. Results showed that SunLec, SoyLec and DATEM elicited a dose- and time-dependent decrease in TEER. RNA-seq analysis indicated that both lecithins upregulated the pathways of response to lipid and cell death at 6.25 mg/ml. Specifically, wound healing was upregulated with SunLec exposure, while cell migration, oxidative stress and angiogenesis pathways were upregulated with SoyLec. DATEM showed increased cell death, regulation of metabolic processes and response to oxygen-related compounds. An increase in type 2 cytokine levels such as IL-4, IL-13 and IL-33 in response to 6.25 mg/ml of SunLec, while 6.25 mg/ml of SoyLec induced production of proinflammatory cytokines (IL-6, IL-18) as well as alarmins (TSLP, IL-33). DATEM induced the production of not only one of the alarmins, TSLP, but also proinflammatory and cell death-related proteins such as caspase 8, IL-18, DDX58 and peroxiredoxins. In conclusion, the present study provides direct evidence on the detrimental effects of food emulsifiers, SunLec, SoyLec and DATEM on intestinal epithelial integrity, due to extensive proinflammatory response of the epithelial cells, namely causing epithelitis.