0479728 - FGÚ 2018 RIV US eng J - Journal Article
Ergang, Peter - Vodička, Martin - Vagnerová, Karla - Moravec, Martin - Kvapilová, Pavlína - Kment, M. - Pácha, Jiří
Inflammation regulates 11 beta-hydroxysteroid dehydrogenase type 1 differentially in specific compartments of the gut mucosal immune system.
Steroids. Roč. 126, Oct 2017 (2017), s. 66-73. ISSN 0039-128X. E-ISSN 1878-5867
R&D Projects: GA ČR(CZ) GAP303/10/0969; GA ČR GA15-07268S
Institutional support: RVO:67985823
Keywords : metabolism of glucocorticoids * cytokine microenvironment * lymphoid organs * colon * Dextran sodium sulfate colitis
OECD category: Physiology (including cytology)
Impact factor: 2.523, year: 2017 ; AIS: 0.637, rok: 2017
DOI: https://doi.org/10.1016/j.steroids.2017.07.007

The bioavailability of glucocorticoids is modulated by enzyme 11 beta-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 TNFa was increased in both the cortex of MLN and ILF, whereas IL-1 beta and IL-10 were only increased in the follicles. No positive effect was observed in the case of IFN gamma and TGF beta. 11HSD1 was positively correlated with TNFa and less strongly with IL-21, IL-1 beta, 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.
Permanent Link: http://hdl.handle.net/11104/0275677