Biogenic Nanoselenium Particles Effectively Attenuate Oxidative Stress-Induced Intestinal Epithelial Barrier Injury by Activating the Nrf2 Antioxidant Pathway

Recombinant antimicrobial peptide microcin J25 (MccJ25) causes potent antimicrobial activity against enterotoxigenic Escherichia coli (ETEC) in vitro; however, independently of this activity, its role in suppressing intestinal inflammation and epithelial barrier injury in vivo remains unclear. We investigated the therapeutic effects of MccJ25 on intestinal inflammation and epithelial barrier dysfunction and the underlying mechanism, using gentamicin for comparison. In a mouse model of intestinal inflammation, therapeutic administration of either MccJ25 or gentamicin after ETEC K88 infection attenuated clinical symptoms, reduced intestinal pathogen colonization, improved intestinal morphology, and decreased inflammatory pathologies and intestinal permeability, ultimately improving the hosts' health. MccJ25 also attenuated ETEC-induced mouse intestinal barrier dysfunction by enhancing tight junction proteins (TJPs). Using the human epithelial cell line Caco-2, we verified the epithelial barrier-strengthening and mucosal injury-alleviating effects of MccJ25 on ETEC infection: increased expression of TJPs by activating the p38/MAPK pathway, balancing the microbiota, and improving short-chain fatty acid concentrations in the cecum of ETEC-infected mice. Although gentamicin and MccJ25 had similar effects in the inflamed gut, MccJ25 was superior to gentamicin with regard to defending the host from ETEC infection. Overall, MccJ25 may be a promising therapeutic drug for treating enteric pathogen-induced intestinal inflammation diseases. K E Y W O R D S gut microbiota, inflamed gut, inflammation diseases, intestinal barrier injury, mice, pathogens infection | 1019 YU et al.

Section: Discussionsupporting

confidence: 92%

Therapeutic administration of the recombinant antimicrobial peptide microcin J25 effectively enhances host defenses against gut inflammation and epithelial barrier injury induced by enterotoxigenic Escherichia coli infection

Wang

Zeng

et al. 2019

“…The transepithelial electrical resistance (TEER) was determined every other day using the epithelial voltohmmeter (EVOM 2 ; World Precision Instruments, Sarasota, FL, USA). When TEER was stable at ;4000 V cm 2 , the IPEC-J2 cells reached the confluence of monolayer, which is consistent with previous studies (26,27). NPA (1 mM) solution was added into the medium of IPEC-J2 monolayer cells along with L. frumenti for 4 h. After treatment, the TEER of IPEC-J2 monolayer cells was measured by the epithelial voltohmmeter.…”

Section: Measurements Of Transepithelial Electrical Resistance and Apsupporting

confidence: 88%

Lactobacillus frumentiimproves antioxidant capacityvianitric oxide synthase 1 in intestinal epithelial cells

Nie

Hou

et al. 2019

Oxidative damages have adverse effects on mammals. Growing studies have focused on exploring new antioxidants. Here, we report that Lactobacillus frumenti increases the total antioxidation capacity activities and decreases the total reactive oxygen species levels in porcine intestinal epithelial cells. Comparative proteomics revealed that expressions of peroxiredoxin 2, isocitrate dehydrogenase 1, NAD(P)H dehydrogenase quinone 1, antioxidant protein 1, and metallothionein‐2A, which are associated with antioxidant defense system, were significantly increased with L. frumenti treatment. In germ‐free mice, L. frumenti treatment also remarkably improves the intestinal antioxidant capacity. We further illustrated that nitric oxide production—mediated by nitric oxide synthase 1 activation is essential for L. frumenti—induced improvements in intestinal epithelial antioxidant capacity and barrier function. This study suggested that L. frumenti may be a potential probiotic used to prevent oxidative stress—induced aging and diseases in mammals.—Nie, Y., Hu, J., Hou, Q., Zheng, W., Zhang, X., Yang, T., Ma, L., Yan, X. Lactobacillus frumenti improves antioxidant capacity via nitric oxide synthase 1 in intestinal epithelial cells. FASEB J. 33, 10705–10716 (2019). http://www.fasebj.org

“…40,41 In the present study, our data showed that ETEC K88 challenge significantly increased the gene abundance and concentrations of IL-1β, IL-6, IL-8, and TNF-α in jejunum of piglets and IPEC-J2 cells. 45,46 Our data clearly showed that ETEC K88 challenge expression of p38 in IPEC-J2 cells. Oxidative stress is a very important mechanism in many potential mechanisms by which toxic substances affect mammalian cells.…”

Section: Discussionmentioning

confidence: 52%

Icariin and its phosphorylated derivatives alleviate intestinal epithelial barrier disruption caused by enterotoxigenic Escherichia coli through modulate p38 MAPK in vivo and in vitro

Xiong

Huang

et al. 2019

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractThe natural product icariin (ICA) and its phosphorylated derivatives (pICA) have been shown to have outstanding anti-inflammatory and antioxidant properties. This study was to explore the protective effects of ICA and pICA on the intestinal epithelium of enterotoxigenic Escherichia coli (ETEC)-induced piglet diarrhea and its underlying mechanisms in vivo and in vitro. ETEC K88 increased pro-inflammatory cytokine expression, activated oxidative stress and inhibited antioxidant enzyme activity, induced phosphorylated p38 MAPK gene and protein expression, disrupted intestinal barrier function, and led to diarrhea in piglets. Pretreatment with ICA and pICA effectively alleviated ETEC-induced intestinal barrier dysfunction in vivo and in vitro. Pretreatment with p38 MAPK inhibitor (SB203580) significantly rescued the IPEC-J2 cells barrier function damaged by ETEC challenge. However, pretreatment with p38 MAPK activator (anisomycin) did not alleviated the IPEC-J2 cells barrier function damaged by ETEC challenge. Our data demonstrated that ICA and pICA regulate the inflammatory response and oxidative stress of intestinal epithelial cells by inhibiting the expression of p38 MAPK, thereby alleviating ETEC K88-induced disruption of intestinal barrier function and intestinal permeability. These findings provide new insights into the prevention and treatment of intestinal barrier dysfunction induced by ETEC K88. K E Y W O R D S enterotoxigenic Escherichia coli K88, icariin, intestinal barrier function, p38 MAPK, phosphorylated icariin 1784 | XIONG et al.