Attenuating Effects of Dieckol on Endothelial Cell Dysfunction via Modulation of Th17/Treg Balance in the Intestine and Aorta of Spontaneously Hypertensive Rats.

Seyeon Oh,Kyunghee Byun,Ji Tae Jang,Kuk Hui Son,Minjung Shim,Myeongjoo Son

doi:10.3390/antiox10020298

Seyeon Oh, Kyunghee Byun + Show 4 more

Open Access

https://doi.org/10.3390/antiox10020298

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Abstract

Disruptions of the Treg/Th17 cell balance and gut barrier function are associated with endothelial dysfunction. Dieckol (DK) obtained from Ecklonia cava and E. cava extract (ECE) decreases blood pressure by reducing inflammation; however, it has not been elucidated whether DK or ECE modulates the Treg/Th17 balance, changes the gut epithelial barrier, or decreases endothelial cell dysfunction. We evaluated the effects of ECE and DK on gut barrier and the Treg/Th17 balance in the intestine and aorta, with regard to endothelial dysfunction, using the spontaneously hypertensive rat (SHR) model. The level of Th17 cells increased and that of Treg cells decreased in the intestine of SHRs compared to normotensive Wistar Kyoto (WKY) rat. These changes were attenuated by ECE or DK treatment. Additionally, the serum IL-17A level increased in SHRs more than WKY; this was decreased by ECE or DK treatment. The level of Treg cells decreased and that of Th17 cells increased in the aorta of SHRs. These changes were attenuated by ECE or DK treatment. The NF-κB and IL-6 levels were increased in SHRs, but these changes were reversed by ECE or DK treatment. Endothelial cell dysfunction, which was evaluated using peNOS/eNOS, nitrate/nitrite ratio, and NADPH oxidase activity, increased in the aorta of SHRs, but was decreased by ECE or DK treatment. The Treg/Th17 balance in the intestine and aorta of SHRs was attenuated and endothelial cell dysfunction was attenuated through the Th17/NF-κB/IL-6 pathway by ECE or DK.

Highlights

IntroductionStructural changes of the gut epithelial barrier lead to the loss of barrier integrity, resulting in uncontrolled permeability of luminal content and allowing harmful substances into the systemic circulation [1]
As a physical barrier, the gut epithelial barrier, composed of epithelium, mucus lining, and junctional proteins, is involved in modulating the absorption of nutrients and limiting the passage of pathogens or unwanted molecules into the systemic circulation [1].Structural changes of the gut epithelial barrier lead to the loss of barrier integrity, resulting in uncontrolled permeability of luminal content and allowing harmful substances into the systemic circulation [1]
Studies have shown that gut permeability, which was evaluated by measuring fluorescein isothiocyanate (FITC)-dextran in the plasma, was increased in adult spontaneously hypertensive rat (SHR) compared with that in age-matched normotensive Wistar Kyoto (WKY) rat [5,6]

Summary

Introduction

Structural changes of the gut epithelial barrier lead to the loss of barrier integrity, resulting in uncontrolled permeability of luminal content and allowing harmful substances into the systemic circulation [1]. Antioxidants 2021, 10, 298 levels of gut junctional proteins such as occludin, tight junction protein 1, and claudin 4 were decreased in SHR compared with the levels in WKY rat [5,6]. These gut junctional proteins are essential for controlling epithelial barrier function, and expression of those proteins are changed in diseases that relate with increased permeability [7]

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Conclusion