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Suppression of Intestinal Epithelial Cell Chemokine Production by Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0389 Is Mediated by Secreted Bioactive Molecules.

ABSTRACT: Host intestinal epithelial cells (IEC) present at the gastrointestinal interface are exposed to pathogenic and non-pathogenic bacteria and their products. Certain probiotic lactic acid bacteria (LAB) have been associated with a range of host-immune modulatory activities including down-regulation of pro-inflammatory gene expression and cytokine production by IEC, with growing evidence suggesting that these bacteria secrete bioactive molecules with immunomodulatory activity. The aim of this study was to determine whether two lactobacilli with immunomodulatory activity [Lactobacillus rhamnosus R0011 (Lr) and Lactobacillus helveticus R0389 (Lh)], produce soluble mediators able to influence IEC responses to Pattern Recognition Receptor (PRR) ligands and pro-inflammatory cytokines [Tumor Necrosis Factor ? (TNF?), Interleukin-1? (IL-1?)], signals inducing IEC chemokine production during infection. To this end, the effects of cell-free supernatants (CFS) from Lr and Lh on IEC production of the pro-inflammatory chemokines interleukin (IL)-8 and cytokine-induced neutrophil chemoattractant 1 (CINC-1) induced by a range of host- or pathogen-derived pro-inflammatory stimuli were determined, and the impact on human HT-29 IEC and a primary IEC line (rat IEC-6) was compared. The Lr-CFS and Lh-CFS did not significantly modulate basal IL-8 production from HT-29 IECs or CINC-1 production from IEC-6 cells. However, both Lr-CFS and Lh-CFS significantly down-regulated IL-8 production from HT-29 IECs challenged with varied PRR ligands. Lr-CFS and Lh-CFS had differential effects on PRR-induced CINC-1 production by rat IEC-6 IECs, with no significant down-regulation of CINC-1 observed from IEC-6 IECs cultured with Lh-CFS. Further analysis of the Lr-CFS revealed down-regulation of IL-8 production induced by the pro-inflammatory cytokines IL-1? and TNF? Preliminary characterization of the bioactive constituent(s) of the Lr-CFS indicates that it is resistant to treatment with DNase, RNase, and an acidic protease, but is sensitive to alterations in pH. Taken together, these results indicate that these lactobacilli secrete bioactive molecules of low molecular weight that may modulate host innate immune activity through interactions with IEC.

SUBMITTER: Jeffrey MP

PROVIDER: S-EPMC6262363 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Suppression of Intestinal Epithelial Cell Chemokine Production by <i>Lactobacillus rhamnosus</i> R0011 and <i>Lactobacillus helveticus</i> R0389 Is Mediated by Secreted Bioactive Molecules.

Jeffrey Michael P MP Strap Janice L JL Jones Taggart Holly H Green-Johnson Julia M JM

Frontiers in immunology 20181114

Host intestinal epithelial cells (IEC) present at the gastrointestinal interface are exposed to pathogenic and non-pathogenic bacteria and their products. Certain probiotic lactic acid bacteria (LAB) have been associated with a range of host-immune modulatory activities including down-regulation of pro-inflammatory gene expression and cytokine production by IEC, with growing evidence suggesting that these bacteria secrete bioactive molecules with immunomodulatory activity. The aim of this study ...[more]

PMID: 30524427

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Project description:Background & Objectives: Identification of news targets for metabolic diseases treatment or prevention was required. In this context, FIAF/ANGPTL4 appeared as a crucial regulator of energy homeostasis. Lactobacilli are often considered to display beneficial effect for their hosts, acting on regulatory pathway. The aim of the present work was to study the effect of several lactobacilli strains on Fiaf gene expression in human intestinal epithelial cells (IECs) and on mice tissues to decipher the underlying mechanisms. Subjects & Methods: Nineteen lactobacilli strains have been tested on HT-29 cells for their ability to regulate Fiaf gene expression by RT-qPCR. In order to determine regulated pathways, we analyzed the whole genome transcript of IECs. We then validate in vivo bacterial effect using C57BL/6 mono-colonized mice fed with normal chow. Results: We identified one strain (L. rhamnosus CNCMI-4317, p<0,001) modulating Fiaf expression in IECs. This regulation relies potentially on bacterial surface-exposed molecules and seems to be PPAR-γ independent and PPAR-α dependent. Functional analysis revealed that most of the significant different expressed genes affected by this strain were involved in cellular function and maintenance, lymphoid tissues structure and development or lipids metabolism. The regulation of immune system and lipids and carbohydrates metabolism was also confirmed by overrepresentation of Gene Ontology terms analysis. In vivo, the strain increased FIAF protein (p<0,05) in the serum and tend to up regulate it in distal small intestine (p=0,14). Moreover, the observed induction of IL-7 (p<0,05) suggested a role on immune cells regulation. Conclusion: We showed that the strain induce Fiaf expression in human IECs and in mice intestine. This bacterial effect is accompanied by modulation of immune response and metabolism providing such a bacterial strain an interesting candidate to modulate metabolic and low grade inflammation disorders.

Dataset Information

Suppression of Intestinal Epithelial Cell Chemokine Production by Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0389 Is Mediated by Secreted Bioactive Molecules.

Publications

Suppression of Intestinal Epithelial Cell Chemokine Production by <i>Lactobacillus rhamnosus</i> R0011 and <i>Lactobacillus helveticus</i> R0389 Is Mediated by Secreted Bioactive Molecules.

Similar Datasets

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