Inflammation regulates 11β-hydroxysteroid dehydrogenase type 1 differentially in specific compartments of the gut mucosal immune system
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
28754259
DOI
10.1016/j.steroids.2017.07.007
PII: S0039-128X(17)30121-6
Knihovny.cz E-resources
- Keywords
- Colon, Cytokine microenvironment, Dextran sodium sulfate colitis, Lymphoid organs, Metabolism of glucocorticoids,
- MeSH
- 11-beta-Hydroxysteroid Dehydrogenase Type 1 genetics metabolism MeSH
- Cytokines metabolism MeSH
- Colitis enzymology genetics immunology MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Gene Expression Regulation, Enzymologic MeSH
- Intestinal Mucosa immunology MeSH
- Inflammation enzymology genetics immunology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 11-beta-Hydroxysteroid Dehydrogenase Type 1 MeSH
- Cytokines MeSH
The bioavailability of glucocorticoids is modulated by enzyme 11β-hydroxysteroid dehydrogenase type 1 (11HSD1), which catalyzes the conversion of inactive 11-oxo-glucocorticoids to active 11-hydroxy-glucocorticoids cortisol and corticosterone and is regulated by pro-inflammatory cytokines. Our aim was to assess the effect of colitis on the expression of 11HSD1 in specific microanatomical compartments of the mucosal immune system. Using qRT-PCR we quantified the expression of 11HSD1 and cytokines in the colon, mesenteric lymph nodes (MLN) and spleen of mice with colitis. Microsamples of the MLN cortex, paracortex and medulla, colonic crypt epithelium (CCE), lamina propria and isolated intestinal lymphoid follicles (ILF) were harvested by laser microdissection, whereas splenic and MLN lymphocytes by flow cytometry. Colitis increased 11HSD1 in the CCE, ILF, and MLN cortex but not in the lamina propria and the MLN paracortex and medulla. Expression of IL-4, IL-21 and TNFα was increased in both the cortex of MLN and ILF, whereas IL-1β and IL-10 were only increased in the follicles. No positive effect was observed in the case of IFNγ and TGFβ. 11HSD1 was positively correlated with TNFα and less strongly with IL-21, IL-1β, and IL-4. Colitis also upregulated the 11HSD1 expression of T cells in the spleen and MLN. The study demonstrates the stimulatory effect of inflammation on local glucocorticoid metabolism only in particular compartments of the mucosal immune system. The correlation between cytokines and 11HSD1 in the ILF and MLN cortex indicates that pro-inflammatory cytokines may amplify glucocorticoid signals in inductive compartments of the mucosal immune system.
2nd Department of Internal Medicine 3rd Faculty of Medicine Charles University Prague Czech Republic
Institute of Physiology Academy of Sciences of the Czech Republic Prague Czech Republic
References provided by Crossref.org
The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine
