Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy
| Autor: | Brenda D. Stride, Anna Kleiman, Jan Tuckermann, François Tronche, Andreas J. R. Habenicht, Günther Schütz, Anett Illing, Wolfgang Schmid, Irmgard Förster, Björn E. Clausen, Rainer Spanbroek, Holger M. Reichardt, Anita Neumann, Richard Moriggl |
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| Přispěvatelé: | Génétique moléculaire, neurophysiologie et comportement, Centre National de la Recherche Scientifique (CNRS), Tronche, François, Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Chemokine
Neutrophils Transgene Anti-Inflammatory Agents Mice Transgenic Dexamethasone Proinflammatory cytokine Mice 03 medical and health sciences Drug Delivery Systems Receptors Glucocorticoid 0302 clinical medicine Immune system Downregulation and upregulation medicine Animals Receptor Cells Cultured 030304 developmental biology Mice Inbred BALB C 0303 health sciences biology Macrophages Monocyte Chemotaxis General Medicine 3. Good health Mice Inbred C57BL medicine.anatomical_structure 030220 oncology & carcinogenesis Dermatitis Allergic Contact Immunology biology.protein Immunosuppressive Agents Research Article |
| Zdroj: | Journal of Clinical Investigation Journal of Clinical Investigation, American Society for Clinical Investigation, 2007, 117 (5), pp.1381-90 The journal of clinical investigation, 117(5):1381–1390 Europe PubMed Central Journal of clinical investigation, 117(5), 1381-1390. The American Society for Clinical Investigation |
| ISSN: | 0021-9738 |
| Popis: | Glucocorticoids (GCs) are widely used in the treatment of allergic skin conditions despite having numerous side effects. Here we use Cre/loxP-engineered tissue- and cell-specific and function-selective GC receptor (GR) mutant mice to identify responsive cell types and molecular mechanisms underlying the antiinflammatory activity of GCs in contact hypersensitivity (CHS). CHS was repressed by GCs only at the challenge phase, i.e., during reexposure to the hapten. Inactivation of the GR gene in keratinocytes or T cells of mutant mice did not attenuate the effects of GCs, but its ablation in macrophages and neutrophils abolished downregulation of the inflammatory response. Moreover, mice expressing a DNA binding-defective GR were also resistant to GC treatment. The persistent infiltration of macrophages and neutrophils in these mice is explained by an impaired repression of inflammatory cytokines and chemokines such as IL-1beta, monocyte chemoattractant protein-1, macrophage inflammatory protein-2, and IFN-gamma-inducible protein 10. In contrast TNF-alpha repression remained intact. Consequently, injection of recombinant proteins of these cytokines and chemokines partially reversed suppression of CHS by GCs. These studies provide evidence that in contact allergy, therapeutic action of corticosteroids is in macrophages and neutrophils and that dimerization GR is required. |
| Databáze: | OpenAIRE |
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