AB0045 Il-17 induced glucocorticoid insensitivity might be dependent on the reduced 11beta-hsd1 enzyme activity

• Published in: Annals of the rheumatic diseases Vol. 76; no. Suppl 2; pp. 1062 - 1063
• Main Authors: Vitiello, M, Kunnathully, V, Orsolini, G, Viapiana, O, Poli, F, Mattè, A, Franceschi, L De, Idolazzi, L, Gatti, D, Rossini, M
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2017
• Subjects: CD14 antigen; CD16 antigen; Enzymatic activity; Enzymes; Glucocorticoids; Hormones; Hydrocortisone; Inflammation; Interleukin 17; Leukocytes (mononuclear); Monocytes; Peripheral blood mononuclear cells
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2017-eular.2681

BackgroundIt 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.ObjectivesTo 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.MethodsPeripheral 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.ResultsMonocytes 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.ConclusionsThe 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 InterestNone declared