Extracellular Vesicles Derived from Kefir Grain Lactobacillus Ameliorate Intestinal Inflammation via Regulation of Proinflammatory Pathway and Tight Junction Integrity.

Eun Ae Kang,Eun Wook Choi,Hyeon-Young Jegal,Byung-Soon Park,Hye-In Choi,Seokwoo Kang,Joo Sung Kim,Seung Wook Hong

doi:10.3390/biomedicines8110522

Eun Ae Kang, Eun Wook Choi + Show 6 more

Open Access

https://doi.org/10.3390/biomedicines8110522

Copy DOI

Abstract

The aim of this study was to demonstrate the anti-inflammatory effect of Lactobacillus kefirgranum PRCC-1301-derived extracellular vesicles (PRCC-1301 EVs) on intestinal inflammation and intestinal barrier function. Human intestinal epithelial cells (IECs) Caco-2 were treated with PRCC-1301 EVs and then stimulated with dextran sulfate sodium (DSS). Real-time RT-PCR revealed that PRCC-1301 EVs inhibited the expression of pro-inflammatory cytokines in Caco-2 cells. PRCC-1301 EVs enhanced intestinal barrier function by maintaining intestinal cell integrity and the tight junction. Loss of Zo-1, claudin-1, and occludin in Caco-2 cells and the colitis tissues was recovered after PRCC-1301 EVs treatment, as evidenced by immunofluorescence analysis. Acute murine colitis was induced using 4% DSS and chronic colitis was generated in piroxicam-treated IL-10-/- mice. PRCC-1301 EVs attenuated body weight loss, colon shortening, and histological damage in acute and chronic colitis models in mice. Immunohistochemistry revealed that phosphorylated NF-κB p65 and IκBα were reduced in the colon tissue sections treated with PRCC-1301 EVs. Our results suggest that PRCC-1301 EVs may have an anti-inflammatory effect on colitis by inhibiting the NF-κB pathway and improving intestinal barrier function.

Highlights

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by chronic recurrent intestinal inflammation
PRCC-1301 Extracellular vesicle (EV) may have an anti-inflammatory effect on colitis by inhibiting the NF-κB pathway and improving intestinal barrier function
ILof theThese colonresults length indicate was reduced, and histopathologic findings and histologic score demonstrate therapeutic effect of PRCC-1301 EVs compared to the vehicle (Figure 3E,F). These results indicate that the PRCC-1301 alleviate dextran sulfate sodium (DSS)-induced colitis and chronic colitis in

Summary

Introduction

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by chronic recurrent intestinal inflammation. IBD is caused by multiple factors such as genetic predispositions, environmental factors, intestinal microbial changes, and excessive immune response [1,2,3]. The pathophysiology of IBD is incompletely understood, intestinal barrier function plays an important role in IBD pathogenesis [4,5,6]. Damage to intestinal epithelial cells compromises integrity and loosens tight junctions (TJs), leading to “leaky gut”. Biomedicines 2020, 8, 522 epithelial barrier can facilitate direct interaction between pro-inflammatory antigenic components in the lumen and the intestinal epithelium [7]. The nuclear factor kappa beta (NF-κB) signaling pathway is one of the major pathophysiologic mechanisms that can promote inflammatory cytokine production [8]. Current treatment options aim to suppress inflammation based on various mechanisms

Objectives

Methods

Conclusion