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AB0045 Il-17 induced glucocorticoid insensitivity might be dependent on the reduced 11beta-hsd1 enzyme activity
  1. M Vitiello1,
  2. V Kunnathully1,
  3. G Orsolini1,
  4. O Viapiana1,
  5. F Poli1,
  6. A Mattè2,
  7. L De Franceschi2,
  8. L Idolazzi1,
  9. D Gatti1,
  10. M Rossini1
  1. 1Rheumatology Unit
  2. 2Internal Medicine Section, University of Verona, Verona, Italy

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

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