Naringenin prevents TNF-α-induced gut-vascular barrier disruption associated with inhibiting the NF-κB-mediated MLCK/p-MLC and NLRP3 pathways
| Autor: | Ruyang Yu, Qilyu Zhou, Zhongjie Liu, Jia Zhong, Ping Liu, Yifei Bian |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Naringenin Myosin light-chain kinase Inflammasomes Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Western blot NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Intestinal Mucosa Cells Cultured Evans Blue Tight Junction Proteins medicine.diagnostic_test Tight junction Chemistry Tumor Necrosis Factor-alpha NF-kappa B food and beverages NF-κB General Medicine Cell biology Rats 030104 developmental biology 030220 oncology & carcinogenesis Flavanones Microvessels TLR4 Tumor necrosis factor alpha Food Science Signal Transduction |
| Zdroj: | Foodfunction. 12(6) |
| ISSN: | 2042-650X |
| Popis: | The microvasculature endothelium accurately regulates the passage of molecules across the gut-vascular barrier (GVB), which plays an essential role in intestinal immunity. Naringenin is reported to have therapeutic potential against several intestinal disorders. However, the effect of naringenin on GVB disruption has been rarely studied. This study aims to investigate the effect of naringenin on GVB function and the potential mechanism. In the present study, the in vitro GVB disruption of rat intestinal microvascular endothelial cells (RIMVEC) was induced by 50 ng mL-1 of tumor necrosis factor-α (TNF-α). The integrity of the in vitro GVB was determined by Evans blue (EB)-albumin efflux assay and trans-endothelial electrical resistance (TER). Meanwhile, the expression of tight junction proteins and the related NF-κB, MLCK/p-MLC and NLRP3 pathways were determined using enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunofluorescence. The results show that naringenin (100 μM) inhibits TNF-α-induced interleukin (IL)-6 hypersecretion, alleviates GVB disruption and mitigates the change in the tight junction protein expression pattern. Naringenin inhibits the GVB-disruption-associated activation of the MLCK/p-MLC system and TLR4/NF-κB/NLRP3 pathways. Furthermore, naringenin shows a similar effect to that of NF-κB inhibitor Bay 11-7082 in reducing the TNF-α-induced activation of NLRP3, p-MLC and secondary GVB disruption. The results suggest that naringenin evidently alleviates TNF-α-induced in vitro GVB disruption via the maintenance of a tight junction protein pattern, partly with the inhibition of the NF-κB-mediated MLCK/p-MLC and NLRP3 pathway activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|