scholarly journals P044 Milk derived exosomes has a therapeutic effect on experimental colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S155-S155
Author(s):  
R Golan-Gerstl ◽  
N Koroukhov ◽  
Y Elbaum Shiff ◽  
I Shilo ◽  
S Reif
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Therapeutic Effect ◽  
Experimental Colitis ◽  
Intestinal Epithelial ◽  
Mice Model ◽  
High Concentration ◽  
Fluorescent Signal ◽  
Proliferation And Differentiation

Abstract Background Inflammatory bowel disease (IBD) is a complex disorder that results from a dysregulated immune response in the gut. Emerging therapy for IBD treatment is mainly focused on regulation of the immune response. Exosomes are nanovesicle packing different molecules such as miRNAs that transfer their cargo to recipient cells. We and others found that mammalian milk contain high concentration of exosomes (milk-derived exosomes, MDE) carrying beneficial miRNAs such as miRNA-148. Furthermore, MDE are taken up by different cell type such as intestinal epithelial cells, modify target gene expression, promote proliferation and differentiation of colon epithelial cells. The aim of this study is to explore the therapeutic effect of MDE on colitis. Methods We used gavage administration of MDE labelled with DiR dye to track their localisation patterns in vivo. The therapeutic effect of MDE on colitis was study in mice model of SDS induced colitis, colon length, histopathological scoring grade, cytokine expression, stool consistency and miRNA expression were analysed. Results Imaging of mouse that have receive labelled MDE revealed an accumulation of fluorescent signal in the intestine. Moreover, fluorescent signal in the intestine and liver is time dependent. MDE reduced the histopathological scoring grade from 5.83 ± 1.47 to 0.6 ± 0.6, p < 0.05. The length of the colon of MDE-treated animals was 7.9 ± 0.19 in comparison to 6.92 ± 0.3 p < 0.05 of the untreated. The weight loss as a result of the colitis was reverted in MDE-treated mice. Likewise, MDE treatment reduced IL-6, TNF-α and caveolin expression from 3.83 to 0.78, 1.59 to 0.86 and 3.52 to 1.1, respectively. Highly expressed miRNAs (miRNA-320, 375, Let-7a and 6073) were found to be more abundant in colon of MDE treatment mice compared with the untreated. Conclusion This study demonstrated that MDE have a therapeutic effect on colitis in vivo. Proving the effect of MDE on colitis will have implications for the potential of adding MDE as a therapeutic nutrient to be included in the formulas for IBD patients.

scholarly journals Ligilactobacillus salivarius Strains Isolated From the Porcine Gut Modulate Innate Immune Responses in Epithelial Cells and Improve Protection Against Intestinal Viral-Bacterial Superinfection

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuhki Indo ◽  
Shugo Kitahara ◽  
Mikado Tomokiyo ◽  
Shota Araki ◽  
Md. Aminul Islam ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Innate Immune ◽  
Intestinal Epithelial ◽  
Innate Immune Responses ◽  
Rotavirus Infection ◽  
Intestinal Infections ◽  
Immune Health

Previously, we constructed a library of Ligilactobacillus salivarius strains from the intestine of wakame-fed pigs and reported a strain-dependent capacity to modulate IFN-β expression in porcine intestinal epithelial (PIE) cells. In this work, we further characterized the immunomodulatory activities of L. salivarius strains from wakame-fed pigs by evaluating their ability to modulate TLR3- and TLR4-mediated innate immune responses in PIE cells. Two strains with a remarkable immunomodulatory potential were selected: L. salivarius FFIG35 and FFIG58. Both strains improved IFN-β, IFN-λ and antiviral factors expression in PIE cells after TLR3 activation, which correlated with an enhanced resistance to rotavirus infection. Moreover, a model of enterotoxigenic E. coli (ETEC)/rotavirus superinfection in PIE cells was developed. Cells were more susceptible to rotavirus infection when the challenge occurred in conjunction with ETEC compared to the virus alone. However, L. salivarius FFIG35 and FFIG58 maintained their ability to enhance IFN-β, IFN-λ and antiviral factors expression in PIE cells, and to reduce rotavirus replication in the context of superinfection. We also demonstrated that FFIG35 and FFIG58 strains regulated the immune response of PIE cells to rotavirus challenge or ETEC/rotavirus superinfection through the modulation of negative regulators of the TLR signaling pathway. In vivo studies performed in mice models confirmed the ability of L. salivarius FFIG58 to beneficially modulate the innate immune response and protect against ETEC infection. The results of this work contribute to the understanding of beneficial lactobacilli interactions with epithelial cells and allow us to hypothesize that the FFIG35 or FFIG58 strains could be used for the development of highly efficient functional feed to improve immune health status and reduce the severity of intestinal infections and superinfections in weaned piglets.

scholarly journals Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 328 ◽  
Author(s):  
Claudio Salaris ◽  
Melania Scarpa ◽  
Marina Elli ◽  
Alice Bertolini ◽  
Simone Guglielmetti ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Plaque Assay ◽  
Immune Response Gene ◽  
Intestinal Epithelial ◽  
Antiviral Immune Response ◽  
Qrt Pcr ◽  
Anti Inflammatory

SARS-CoV-2 is a newly emerging virus that currently lacks curative treatments. Lactoferrin (LF) is a naturally occurring non-toxic glycoprotein with broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. In this study, we assessed the potential of LF in the prevention of SARS-CoV-2 infection in vitro. Antiviral immune response gene expression was analyzed by qRT-PCR in uninfected Caco-2 intestinal epithelial cells treated with LF. An infection assay for SARS-CoV-2 was performed in Caco-2 cells treated or not with LF. SARS-CoV-2 titer was determined by qRT-PCR, plaque assay and immunostaining. Inflammatory and anti-inflammatory cytokine production was determined by qRT-PCR. LF significantly induced the expression of IFNA1, IFNB1, TLR3, TLR7, IRF3, IRF7 and MAVS genes. Furthermore, LF partially inhibited SARS-CoV-2 infection and replication in Caco-2 intestinal epithelial cells. Our in vitro data support LF as an immune modulator of the antiviral immune response with moderate effects against SARS-CoV-2 infection.

scholarly journals Characterization of Weissella viridescens UCO-SMC3 as a Potential Probiotic for the Skin: Its Beneficial Role in the Pathogenesis of Acne Vulgaris

2021 ◽  
Vol 9 (7) ◽  
pp. 1486
Author(s):  
Marcela Espinoza-Monje ◽  
Jorge Campos ◽  
Eduardo Alvarez Villamil ◽  
Alonso Jerez ◽  
Stefania Dentice Maidana ◽  
...  
Keyword(s):  
Immune Response ◽  
Oral Treatment ◽  
Acne Vulgaris ◽  
Topical Administration ◽  
In Vivo Studies ◽  
Mice Model ◽  
Cutibacterium Acnes ◽  
Snail Helix Aspersa

Previously, we isolated lactic acid bacteria from the slime of the garden snail Helix aspersa Müller and selected Weissella viridescens UCO-SMC3 because of its ability to inhibit in vitro the growth of the skin-associated pathogen Cutibacterium acnes. The present study aimed to characterize the antimicrobial and immunomodulatory properties of W. viridescens UCO-SMC3 and to demonstrate its beneficial effect in the treatment of acne vulgaris. Our in vitro studies showed that the UCO-SMC3 strain resists adverse gastrointestinal conditions, inhibits the growth of clinical isolates of C. acnes, and reduces the adhesion of the pathogen to keratinocytes. Furthermore, in vivo studies in a mice model of C. acnes infection demonstrated that W. viridescens UCO-SMC3 beneficially modulates the immune response against the skin pathogen. Both the oral and topical administration of the UCO-SCM3 strain was capable of reducing the replication of C. acnes in skin lesions and beneficially modulating the inflammatory response. Of note, orally administered W. viridescens UCO-SMC3 induced more remarkable changes in the immune response to C. acnes than the topical treatment. However, the topical administration of W. viridescens UCO-SMC3 was more efficient than the oral treatment to reduce pathogen bacterial loads in the skin, and effects probably related to its ability to inhibit and antagonize the adhesion of C. acnes. Furthermore, a pilot study in acne volunteers demonstrated the capacity of a facial cream containing the UCO-SMC3 strain to reduce acne lesions. The results presented here encourage further mechanistic and clinical investigations to characterize W. viridescens UCO-SMC3 as a probiotic for acne vulgaris treatment.

scholarly journals Expression of lysophosphatidic acid receptor 5 is necessary for the regulation of intestinal Na+/H+ exchanger 3 by lysophosphatidic acid in vivo

2018 ◽  
Vol 315 (4) ◽  
pp. G433-G442 ◽  
Author(s):  
Kayte A. Jenkin ◽  
Peijian He ◽  
C. Chris Yun
Keyword(s):  
Epithelial Cells ◽  
Lysophosphatidic Acid ◽  
Direct Evidence ◽  
Intestinal Epithelial Cells ◽  
Regulatory Role ◽  
Intestinal Epithelial ◽  
Fluid Absorption ◽  
Wild Type

Lysophosphatidic acid (LPA) is a bioactive lipid molecule, which regulates a broad range of pathophysiological processes. Recent studies have demonstrated that LPA modulates electrolyte flux in the intestine, and its potential as an antidiarrheal agent has been suggested. Of six LPA receptors, LPA5 is highly expressed in the intestine. Recent studies by our group have demonstrated activation of Na+/H+ exchanger 3 (NHE3) by LPA5. However, much of what has been elucidated was achieved using colonic cell lines that were transfected to express LPA5. In the current study, we engineered a mouse that lacks LPA5 in intestinal epithelial cells, Lpar5ΔIEC, and investigated the role of LPA5 in NHE3 regulation and fluid absorption in vivo. The intestine of Lpar5ΔIEC mice appeared morphologically normal, and the stool frequency and fecal water content were unchanged compared with wild-type mice. Basal rates of NHE3 activity and fluid absorption and total NHE3 expression were not changed in Lpar5ΔIEC mice. However, LPA did not activate NHE3 activity or fluid absorption in Lpar5ΔIEC mice, providing direct evidence for the regulatory role of LPA5. NHE3 activation involves trafficking of NHE3 from the terminal web to microvilli, and this mobilization of NHE3 by LPA was abolished in Lpar5ΔIEC mice. Dysregulation of NHE3 was specific to LPA, and insulin and cholera toxin were able to stimulate and inhibit NHE3, respectively, in both wild-type and Lpar5ΔIEC mice. The current study for the first time demonstrates the necessity of LPA5 in LPA-mediated stimulation of NHE3 in vivo. NEW & NOTEWORTHY This study is the first to assess the role of LPA5 in NHE3 regulation and fluid absorption in vivo using a mouse that lacks LPA5 in intestinal epithelial cells, Lpar5ΔIEC. Basal rates of NHE3 activity and fluid absorption, and total NHE3 expression were not changed in Lpar5ΔIEC mice. However, LPA did not activate NHE3 activity or fluid absorption in Lpar5ΔIEC mice, providing direct evidence for the regulatory role of LPA5.

Progastrin1–80stimulates growth of intestinal epithelial cells in vitro via high-affinity binding sites

2003 ◽  
Vol 284 (2) ◽  
pp. G328-G339 ◽  
Author(s):  
P. Singh ◽  
X. Lu ◽  
S. Cobb ◽  
B. T. Miller ◽  
N. Tarasova ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Binding Sites ◽  
Intestinal Epithelial Cells ◽  
Full Length ◽  
Intestinal Epithelial ◽  
Growth Effects ◽  
High Affinity ◽  
Significant Difference

Proliferation and carcinogenesis of the large intestinal epithelial cells (IEC) cells is significantly increased in transgenic mice that overexpress the precursor progastrin (PG) peptide. It is not known if the in vivo growth effects of PG on IEC cells are mediated directly or indirectly. Full-length recombinant human PG (rhPG1–80) was generated to examine possible direct effects of PG on IEC cells. Surprisingly, rhPG (0.1–1.0 nM) was more effective than the completely processed gastrin 17 (G17) peptide as a growth factor. Even though IEC cells did not express CCK1and CCK2receptors (-R), fluorescently labeled G17 and Gly-extended G17 (G-Gly) were specifically bound to the cells, suggesting the presence of binding proteins other than CCK1-R and CCK2-R on IEC cells. High-affinity ( Kd= 0.5–1.0 nM) binding sites for125I-rhPG were discovered on IEC cells that demonstrated relative binding affinity for gastrin-like peptides in the order PG ≥ COOH-terminally extended G17 ≥ G-Gly > G17 > *CCK-8 (* significant difference; P< 0.05). In conclusion, our studies demonstrate for the first time direct growth effects of the full-length precursor peptide on IEC cells in vitro that are apparently mediated by the high-affinity PG binding sites that were discovered on these cells.

Nondigestible oligosaccharides exert nonprebiotic effects on intestinal epithelial cells enhancing the immune response via activation of TLR4-NFκB

2013 ◽  
Vol 58 (2) ◽  
pp. 384-393 ◽  
Author(s):  
Mercedes Ortega-González ◽  
Borja Ocón ◽  
Isabel Romero-Calvo ◽  
Andrea Anzola ◽  
Emilia Guadix ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial

W1612 Apical Exposure of Intestinal Epithelial Cells to Lactobacilli But Not Bifidobacteria Enhances the Effector Immune Response In Vitro

2009 ◽  
Vol 136 (5) ◽  
pp. A-702
Author(s):  
Els van Hoffen ◽  
Nicoline M. Korthagen ◽  
Sander de Kivit ◽  
Bastiaan Schouten ◽  
Bart Bardoel ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Effector Immune Response ◽  
Immune Response In Vitro

Comparison of gene expression and activation of transcription factors in organoid-derived monolayer intestinal epithelial cells and organoids

2021 ◽  
Author(s):  
Yu Takahashi ◽  
Yu Inoue ◽  
Keitaro Kuze ◽  
Shintaro Sato ◽  
Makoto Shimizu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Gene Expression Regulation ◽  
Intestinal Epithelial Cells ◽  
Three Dimensional ◽  
Culture Conditions ◽  
Dependent Manner ◽  
Intestinal Epithelial

Abstract Intestinal organoids better represent in vivo intestinal properties than conventionally used established cell lines in vitro. However, they are maintained in three-dimensional culture conditions that may be accompanied by handling complexities. We characterized the properties of human organoid-derived two-dimensionally cultured intestinal epithelial cells (IECs) compared with those of their parental organoids. We found that the expression of several intestinal markers and functional genes were indistinguishable between monolayer IECs and organoids. We further confirmed that their specific ligands equally activate intestinal ligand-activated transcriptional regulators in a dose-dependent manner. The results suggest that culture conditions do not significantly influence the fundamental properties of monolayer IECs originating from organoids, at least from the perspective of gene expression regulation. This will enable their use as novel biological tools to investigate the physiological functions of the human intestine.

Sign in / Sign up

Export Citation Format

Share Document