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Allergy 61, 7 (2006) 886-90
Dexamethasone and IL-10 stimulate glucocorticoid-induced leucine zipper synthesis by human mast cells.
V. Godot 1, G. Garcia 2, 3, 4, 5, F. Capel, Michel Arock 6, I. Durand-Gasselin 1, M. L. Asselin-Labat, D. Emilie 1, 7, 8, M. Humbert 9
(07/2006)

BACKGROUND: Glucocorticoids (GCs) decrease tissue mast cell (MC) number and prevent their activation via their high-affinity IgE receptor. Glucocorticoid-induced leucine zipper (GILZ) is one of the GC-induced genes, which inhibits the functions of the transcriptional activators AP-1 and NF-kappaB. GILZ appears to be a critical actor in the anti-inflammatory and immunosuppressive effects of GCs in human T lymphocytes, macrophages and dendritic cells. AIMS OF THE STUDY: We investigated whether GILZ was produced by human MCs and whether GILZ synthesis was stimulated by GCs. We also investigated whether GILZ production was modulated by (i) IL-10, because of its common immunosuppressive properties with GCs, (ii) histamine because of its pro-inflammatory properties and (iii) IL-4 and IL-5 because of their ability to favour MC survival and proliferation with SCF. METHODS: The human MC lines HMC-1 5C6 and LAD-2, and cord blood-derived MCs (CB-MCs) were cultured alone or in the presence of GCs, IL-10, histamine, IL-4 or IL-5. The expression of GILZ was evaluated by using RT-PCR, Western blotting or immunocytochemistry. RESULTS: We found that human MC lines and CB-MCs constitutively produce GILZ. We also show that GCs and IL-10 stimulate GILZ production by human MCs. Our present results indicate that histamine, IL-4 and IL-5 alone or in combination with SCF do not downregulate GILZ production by MCs. CONCLUSIONS: These results show that GCs and IL-10 stimulate GILZ production by human MCs. As GILZ mediates anti-inflammatory effects of GCs in immune cells, we speculate that GILZ could account for the deactivation of MCs by GCs and IL-10.
1 :  Cytokines, chimiokines et immunopathologie
INSERM : U764 – IFR13 – Université Paris XI - Paris Sud
2 :  Laboratoire Francis PERRIN (LFP - URA 2453)
CNRS : URA2453 – CEA : DSM/IRAMIS
3 :  Centre d'étude des environnements terrestre et planétaires (CETP)
CNRS : UMR8639 – INSU – Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
4 :  Laboratoire de géobiologie, biochronologie et paléontologie humaine (LGBPH)
CNRS : UMR6046 – Université de Poitiers
5 :  Laboratoire pour l'utilisation du rayonnement électromagnétique (LURE)
CNRS : UMR130 – CEA – MENRT
6 :  Laboratoire de Biotechnologie et Pharmacologie génétique Appliquée (LBPA)
CNRS : UMR8113 – École normale supérieure [ENS] - Cachan
7 :  Service de microbiologie, immunologie biologique
Assistance publique - Hôpitaux de Paris (AP-HP) – Hôpital Antoine Béclère – Université Paris XI - Paris Sud
8 :  Laboratoire de Physique et Mécanique Textiles (LPMT)
ENSITM – Université de Haute Alsace - Mulhouse
9 :  Laboratoire d'étude des textures et application aux matériaux (LETAM)
CNRS : UMR7078 – Université Paul Verlaine - Metz
Sciences du Vivant/Immunologie