Formoterol synergy with des-ciclesonide inhibits IL-4 expression in IgE/antigen-induced mast cells by inhibiting JNK activation
| Autor: | Yong-liang Jia, Xin-wei Dong, Hui-juan Shen, Yan-hong Sun, Qiang-min Xie, Ling-tian Ge, Jun-xia Jiang, Yun Sun |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.drug_class
Ciclesonide Pharmacology Immunoglobulin E Histamine Release chemistry.chemical_compound Antigen Adrenal Cortex Hormones Pregnenediones Cell Line Tumor Formoterol Fumarate medicine Animals Mast Cells RNA Messenger Phosphorylation Adrenergic beta-2 Receptor Agonists Protein Kinase Inhibitors Histamine Production Interleukin 4 Interleukin-13 Dose-Response Relationship Drug biology business.industry JNK Mitogen-Activated Protein Kinases Drug Synergism Serum Albumin Bovine Rats respiratory tract diseases Enzyme Activation Gene Expression Regulation chemistry biology.protein Corticosteroid Drug Therapy Combination Interleukin-4 Formoterol business Dinitrophenols hormones hormone substitutes and hormone antagonists Histamine Signal Transduction medicine.drug |
| Zdroj: | European Journal of Pharmacology. 761:161-167 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2015.05.008 |
| Popis: | Inhaled corticosteroid (ICS) therapy in combination with long-acting β-adrenergic agonists (LABA) is the most important treatment for allergic asthma, although the mechanism still remains unclear. However, mast cells play a central role in the pathogenesis of asthma. In this study, we explored the sole or synergetic effects of des-ciclesonide (ICS) and formoterol (LABA) on the cytokines IL-4 and IL-13 and on histamine release from mast cells (RBL-2H3 cells). We found that des-ciclesonide (0.1, 1 and 10 nM) and formoterol (0.1, 1 and 10 μM) alone attenuated DNP–BSA-induced IL-4 and IL-13 production, respectively, in a concentration-dependent manner in DNP-IgE-sensitized mast cells. Des-ciclesonide (0.2 nM) and formoterol (1 μM) alone also reduced histamine production. However, the combination of des-ciclesonide (0.2 nM) and formoterol (1 μM) had a synergistic inhibition effect on IL-4 mRNA expression and protein production but not IL-13 and histamine release. The JNK inhibitor SP600125 (10 μM) inhibited antigen-induced mRNA expression and protein production of IL-4. Des-ciclesonide and formoterol alone inhibited the activation of JNK in a concentration-dependent manner, and the combination of des-ciclesonide (0.2 nM) and formoterol (1 μM) exhibited greater inhibition effect compared with des-ciclesonide (0.2 nM) or formoterol (1 μM) alone. Taken together, these synergistic effects on mast cells might provide the rationale for the development of the most recent ICS/LABA combination approved for asthma therapy. |
| Databáze: | OpenAIRE |
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