Abstract |
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 10nM) and formoterol (0.1, 1 and 10μM) 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 (0.2nM) and formoterol (1μM) alone also reduced histamine production. However, the combination of des-ciclesonide (0.2nM) and formoterol (1μM) had a synergistic inhibition effect on IL-4 mRNA expression and protein production but not IL-13 and histamine release. The JNK inhibitor SP600125 (10μM) 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 (0.2nM) and formoterol (1μM) exhibited greater inhibition effect compared with des-ciclesonide (0.2nM) or formoterol (1μM) 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.
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Authors | Yan-hong Sun, Ling-tian Ge, Jun-xia Jiang, Hui-juan Shen, Yong-liang Jia, Xin-wei Dong, Yun Sun, Qiang-min Xie |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 761
Pg. 161-7
(Aug 15 2015)
ISSN: 1879-0712 [Electronic] Netherlands |
PMID | 26003274
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier B.V. All rights reserved. |
Chemical References |
- Adrenal Cortex Hormones
- Adrenergic beta-2 Receptor Agonists
- Dinitrophenols
- Interleukin-13
- Pregnenediones
- Protein Kinase Inhibitors
- RNA, Messenger
- dinitrophenyl-bovine serum albumin
- Interleukin-4
- Serum Albumin, Bovine
- Immunoglobulin E
- desisobutyrylciclesonide
- JNK Mitogen-Activated Protein Kinases
- Formoterol Fumarate
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Topics |
- Adrenal Cortex Hormones
(pharmacology)
- Adrenergic beta-2 Receptor Agonists
(pharmacology)
- Animals
- Cell Line, Tumor
- Dinitrophenols
(immunology)
- Dose-Response Relationship, Drug
- Drug Synergism
- Drug Therapy, Combination
- Enzyme Activation
- Formoterol Fumarate
(pharmacology)
- Gene Expression Regulation
- Histamine Release
(drug effects)
- Immunoglobulin E
(immunology)
- Interleukin-13
(metabolism)
- Interleukin-4
(genetics, metabolism)
- JNK Mitogen-Activated Protein Kinases
(antagonists & inhibitors, metabolism)
- Mast Cells
(drug effects, enzymology, immunology)
- Phosphorylation
- Pregnenediones
(pharmacology)
- Protein Kinase Inhibitors
(pharmacology)
- RNA, Messenger
(metabolism)
- Rats
- Serum Albumin, Bovine
(immunology)
- Signal Transduction
(drug effects)
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