Autophagy: A Novel Mechanism Involved in the Anti-Inflammatory Abilities of Probiotics.
Adenine
/ analogs & derivatives
Animals
Autophagy
Autophagy-Related Proteins
Bifidobacterium
/ physiology
Bone Marrow Cells
/ cytology
Carrier Proteins
/ genetics
Chemokines
/ genetics
Colitis
/ chemically induced
Cytokines
/ genetics
Dendritic Cells
/ cytology
Female
Humans
Lactobacillus
/ physiology
Leukocytes, Mononuclear
/ cytology
Macrolides
/ pharmacology
Mice
Mice, Inbred BALB C
Mice, Knockout
Probiotics; Inflammatory bowel diseases; Autophagy; Inflammation
Journal
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221
Informations de publication
Date de publication:
2019
2019
Historique:
accepted:
22
10
2019
entrez:
25
10
2019
pubmed:
28
10
2019
medline:
26
11
2019
Statut:
ppublish
Résumé
Deregulation of the complex interaction among host genetics, gut microbiota and environmental factors on one hand and aberrant immune responses on the other hand, are known to be associated with the development of inflammatory bowel disease. Recent studies provided strong evidence that autophagy plays a key role in the etiology of Crohn's disease (CD). Probiotics may exhibit many therapeutic properties, including anti-inflammatory abilities. While successful results have been obtained in ulcerative colitis patients, probiotics remain inefficient in CD for unknown reason. It remains therefore important to better understand their molecular mechanisms of action. The activation of autophagy was examined by stimulating bone marrow-derived dendritic cells by the bacteria, followed by confocal microscopy and western blot analysis. The impact of blocking in vitro autophagy was performed in peripheral blood mononuclear cells using 3-methyl adenine or bafilomycin followed by cytokine secretion measurement by ELISA. The role of autophagy in the anti-inflammatory capacities of the bacterial strains was evaluated in vivo using an acute trinitrobenzene sulfonic acid-induced murine model of colitis. The impact of BMDC was evaluated by adoptive transfer, notably using bone marrow cells derived from autophagy-related 16-like 1-deficient mice. We showed that selected lactobacilli and bifidobacteria are able to induce autophagy activation in BMDCs. Blocking in vitro autophagy abolished the capacity of the strains to induce the release of the anti-inflammatory cytokine interleukin-10, while it exacerbated the secretion of the pro-inflammatory cytokine interleukin-1β. We confirmed in the TNBS-induced mouse model of colitis that autophagy is involved in the protective capacity of these selected strains, and showed that dendritic cells are involved in this process. We propose autophagy as a novel mechanism involved in the regulatory capacities of probiotics.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
Deregulation of the complex interaction among host genetics, gut microbiota and environmental factors on one hand and aberrant immune responses on the other hand, are known to be associated with the development of inflammatory bowel disease. Recent studies provided strong evidence that autophagy plays a key role in the etiology of Crohn's disease (CD). Probiotics may exhibit many therapeutic properties, including anti-inflammatory abilities. While successful results have been obtained in ulcerative colitis patients, probiotics remain inefficient in CD for unknown reason. It remains therefore important to better understand their molecular mechanisms of action.
METHODS
METHODS
The activation of autophagy was examined by stimulating bone marrow-derived dendritic cells by the bacteria, followed by confocal microscopy and western blot analysis. The impact of blocking in vitro autophagy was performed in peripheral blood mononuclear cells using 3-methyl adenine or bafilomycin followed by cytokine secretion measurement by ELISA. The role of autophagy in the anti-inflammatory capacities of the bacterial strains was evaluated in vivo using an acute trinitrobenzene sulfonic acid-induced murine model of colitis. The impact of BMDC was evaluated by adoptive transfer, notably using bone marrow cells derived from autophagy-related 16-like 1-deficient mice.
RESULTS
RESULTS
We showed that selected lactobacilli and bifidobacteria are able to induce autophagy activation in BMDCs. Blocking in vitro autophagy abolished the capacity of the strains to induce the release of the anti-inflammatory cytokine interleukin-10, while it exacerbated the secretion of the pro-inflammatory cytokine interleukin-1β. We confirmed in the TNBS-induced mouse model of colitis that autophagy is involved in the protective capacity of these selected strains, and showed that dendritic cells are involved in this process.
CONCLUSION
CONCLUSIONS
We propose autophagy as a novel mechanism involved in the regulatory capacities of probiotics.
Substances chimiques
Atg16l1 protein, mouse
0
Autophagy-Related Proteins
0
Carrier Proteins
0
Chemokines
0
Cytokines
0
Macrolides
0
bafilomycin A
116764-51-3
3-methyladenine
5142-23-4
Adenine
JAC85A2161
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
774-793Subventions
Organisme : Association François Aupetit
Pays : France
Organisme : Institut Pasteur de Lille
Pays : France
Organisme : Centre National de la Recherche Scientifique (CNRS)
Pays : France
Organisme : University of Lille
Pays : France
Organisme : ImaginEx Biomed project, Agence Nationale de la Recherche
ID : ANR-10-EQPX-04-01
Pays : France
Informations de copyright
© Copyright by the Author(s). Published by Cell Physiol Biochem Press.
Déclaration de conflit d'intérêts
The authors declare that they have no conflicts of interests.