Dominance of the strongest: Inflammatory cytokines versus glucocorticoids |
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| Affiliation: | 1. Department for Molecular Biomedical Research, Flanders Institute for Biotechnology, B9052 Ghent, Belgium;2. Department of Biomedical Molecular Biology, Ghent University, B9052 Ghent, Belgium;1. Department of Psychology, Hood College, Frederick, MD 21701, USA;2. Department of Psychology, Kent State University, Kent, OH 44242-0001, USA;1. LERMA, UMR 8112, Observatoire de Paris, UPMC, Université Cergy-Pontoise, ENS, CNRS, 5 Place Jules Janssen, 92195 Meudon, France;2. Institute of Physics of ASCR, Na Slovance 2, 182 21 Prague 8, Czech Republic;3. Laboratoire de Physique des Plasmas, UMR 7648, Ecole Polytechnique, UPMC, CNRS, 91128 Palaiseau, France;4. Department of Physical Electronics, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, Brehova 7, 115 19 Prague 1, Czech Republic;5. The Blackett Laboratory, Imperial College, Prince Consort Road, London SW7 2AZ, UK;6. GEPI, UMR 8111, Observatoire de Paris, Université Paris Diderot, CNRS, 5 place Jules Janssen, 92195 Meudon, France;7. SYRTE, UMR 8630, Observatoire de Paris, UMPC, CNRS, 61 Avenue de l''Observatoire, 75014 Paris, France;8. IRFU/Service d ''Astrophysique, CEA-Saclay, 91191 Gif sur Yvette, France;1. Lomonosov Moscow State University Skobeltsyn Institute of Nuclear Physics (MSU SINP), 1(2) Leninskie Gory, 119234 Moscow, Russian Federation;2. Solar Wind Ltd., Tamanskaya 180, 350040 Krasnodar, Russian Federation;3. Ioffe Physical-Technical Institute, Polytechnicheskaya 26, 194021 St. Petersburg, Russian Federation;1. The George Washington University, Washington, DC 20052, USA;2. G.I. Budker Institute of Nuclear Physics, 630090 Novosibirsk, Russia;3. Hebrew University of Jerusalem, Jerusalem, 91904, Israel |
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| Abstract: | Pro-inflammatory cytokines are involved in the pathogenesis of many inflammatory diseases, and the excessive expression of many of them is normally counteracted by glucocorticoids (GCs), which are steroids that bind to the glucocorticoid receptor (GR). Hence, GCs are potent inhibitors of inflammation, and they are widely used to treat inflammatory diseases, such as asthma, rheumatoid arthritis and inflammatory bowel disease. However, despite the success of GC therapy, many patients show some degree of GC unresponsiveness, called GC resistance (GCR). This is a serious problem because it limits the full therapeutic exploitation of the anti-inflammatory power of GCs. Patients with reduced GC responses often have higher cytokine levels, and there is a complex interplay between GCs and cytokines: GCs downregulate pro-inflammatory cytokines while cytokines limit GC action. Treatment of inflammatory diseases with GCs is successful when GCs dominate. But when cytokines overrule the anti-inflammatory actions of GCs, patients become GC insensitive. New insights into the molecular mechanisms of GR-mediated actions and GCR are needed for the design of more effective GC-based therapies. |
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| Keywords: | Inflammation Cytokines Glucocorticoid receptor Glucocorticoid resistance |
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