A recombinant glucocorticoid-induced leucine zipper protein ameliorates symptoms of dextran sulfate sodium-induced colitis by improving intestinal permeability.
Animals
Anti-Inflammatory Agents
/ administration & dosage
Antigens, Differentiation, B-Lymphocyte
/ metabolism
Colitis
/ chemically induced
Cytokines
/ metabolism
Dexamethasone
/ administration & dosage
Dextran Sulfate
/ adverse effects
Disease Models, Animal
Histocompatibility Antigens Class II
/ metabolism
Intestinal Mucosa
/ drug effects
Male
Mice
Mice, Inbred C57BL
Permeability
/ drug effects
Recombinant Fusion Proteins
/ administration & dosage
Signal Transduction
/ drug effects
Trans-Activators
/ genetics
Transcription Factors
/ administration & dosage
Treatment Outcome
Up-Regulation
/ drug effects
Zonula Occludens-1 Protein
/ metabolism
GILZ
colitis
dysbiosis
glucocorticoids
microbiota
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
06
09
2021
received:
11
05
2021
accepted:
09
09
2021
entrez:
6
10
2021
pubmed:
7
10
2021
medline:
16
11
2021
Statut:
ppublish
Résumé
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders characterized by relapsing intestinal inflammation, but many details of pathogenesis remain to be fully unraveled. Glucocorticoid (GC)-induced leucine zipper (GILZ) is a mediator of the anti-inflammatory effects of GCs, the most powerful drugs for IBD treatment, but they cause several unwanted side effects. The fusion protein TAT-GILZ has been successfully used in some pre-clinical models of inflammatory and autoimmune diseases. To test the efficacy of TAT-GILZ for treating dextran sulfate sodium (DSS)-induced colitis and explore its impact on the gut microbiome, colitis was induced by DSS in C57BL/6J mice and treated with TAT-GILZ or dexamethasone. Various hallmarks of colitis were analyzed, including disease activity index, gut permeability, and expression of pro-inflammatory cytokines and tight junction proteins. TAT-GILZ treatment showed a therapeutic effect when administered after the onset of colitis. Its efficacy was associated with improved gut permeability, as evidenced by zonula occludens-1 and CD74 upregulation in inflamed colonic tissue. TAT-GILZ also ameliorated the changes in the gut microbiota induced by the DSS, thus potentially providing an optimal environment for colonization of the mucosa surface by beneficial bacteria. Overall, our results demonstrated for the first time that TAT-GILZ treatment proved effective after disease onset allowing restoration of gut permeability, a key pathogenic feature of colitis. Additionally, TAT-GILZ restored gut dysbiosis, thereby contributing to healing mechanisms. Interestingly, we found unprecedented effects of exogenous GILZ that did not overlap with those of GCs.
Identifiants
pubmed: 34613638
doi: 10.1096/fj.202100778RRRR
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Antigens, Differentiation, B-Lymphocyte
0
Cytokines
0
Dsip1 protein, mouse
0
Histocompatibility Antigens Class II
0
Recombinant Fusion Proteins
0
Trans-Activators
0
Transcription Factors
0
Zonula Occludens-1 Protein
0
invariant chain
0
Dexamethasone
7S5I7G3JQL
Dextran Sulfate
9042-14-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21950Informations de copyright
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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