AB0045 Il-17 induced glucocorticoid insensitivity might be dependent on the reduced 11beta-hsd1 enzyme activity. (15th June 2017)

• Record Type: Journal Article
• Authors: Vitiello, M; Kunnathully, V; Orsolini, G; Viapiana, O; Poli, F; Mattè, A; Franceschi, L De; Idolazzi, L; Gatti, D; Rossini, M
• Is Part Of: Annals of the rheumatic diseases. Volume 76(2017)Supplement 2
• Page Start: 1062
• Page End: 1063
• Publication Date: 2017-06-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2017-eular.2681
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: It has been demonstrated that IL-17A is able to induce GC insensitivity. Although several studies have reported the role of IL-17 in GC insensitivity the mechanism underlying remains still largely unclear. Objectives: To understand the effects of interleukin-17 (IL-17) on the enzyme 11β-hydroxysteroid dehydrogenases (11β-HSDs) in the two main classes of monocytes, CD14 and CD16. Methods: Peripheral Blood Mononuclear Cells (PBMCs) were isolated from 5 healthy donors and were sorted into CD14 and CD16 subpopulations using cell sorting. Effect of IL-17 on 11β-HSD1 enzyme activity was measured in terms of conversion of cortisone to cortisol in sorted and unsorted monocytes using Homogeneous Time-Resolved Fluorescence (HTRF). The direct involvement of 11β-HSD1 in the conversion of cortisone to cortisol was confirmed using carbenoxolone, an inhibitor of 11β-HSD1. Results: Monocytes showed a concentration-dependent decrease in the 11β-HSD1 enzyme activity when incubated with increasing concentrations of IL-17. CD14 and CD16 cells stimulated similarly with IL-17 showed a significant difference in the enzyme activity between the untreated and stimulated cells in all treatment groups. However, a dose dependent decrease was observed only in case of CD14 cells. Both unsorted monocytes and monocyte sub-populations showed a significant decrease in the concentration of cortisol measured when co-incubated with carbenoxolone, indicative of the direct involvement of 11β-HSD1 enzyme in the conversion of cortisone to cortisol. Conclusions: The results of this study showed that IL-17 induced GC insensitivity might be dependent on the reduced 11β-HSD1 enzyme activity in inflammatory conditions. We showed that the pro-inflammatory cytokine IL-17 causes a significant decrease in the 11β-HSD1 enzyme activity. Disclosure of Interest: None declared