ArticleBritish journal of clinical pharmacology2015
Corticosteroid insensitive alveolar macrophages from asthma patients; synergistic interaction with a p38 mitogen-activated protein kinase (MAPK) inhibitor.
Article in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 27 citations in OpenAlex.
- Perinatal glucocorticoid sensitivity in the preterm newborn: molecular mechanisms, endogenous determinants, and clinical implications.Frontiers in endocrinology · 2025Review
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- Modified Gexiazhuyu decoction alleviates chronic salpingitis p38 signaling pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2022Article
- SB203580-A Potent p38 MAPK Inhibitor Reduces the Profibrotic Bronchial Fibroblasts Transition Associated with Asthma.International journal of molecular sciences · 2021Article
- Identification and treatment of T2-low asthma in the era of biologics.ERJ open research · 2021Review
- Oxidative Imbalance as a Crucial Factor in Inflammatory Lung Diseases: Could Antioxidant Treatment Constitute a New Therapeutic Strategy?Oxidative medicine and cellular longevity · 2021Review
- Potential Role of Mast Cells in Regulating Corticosteroid Insensitivity in Severe Asthma.Advances in experimental medicine and biology · 2021Article
- Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling Pathway.Frontiers in physiology · 2021Article
- Interleukin-35 sensitizes monocytes from patients with asthma to glucocorticoid therapy by regulating p38 MAPK.Experimental and therapeutic medicine · 2020Article
- P38 MAPK and glucocorticoid receptor crosstalk in bronchial epithelial cells.Journal of molecular medicine (Berlin, Germany) · 2020Article
- [Pathogenesis of steroid-resistant asthma and the influence of vitamin D].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2019Review
- p38 MAPK activity is associated with the histological degree of interstitial fibrosis in IgA nephropathy patients.PloS one · 2019Article
- Mechanisms of corticosteroid insensitivity in COPD alveolar macrophages exposed to NTHi.Respiratory research · 2017Article
- Chemoattractant concentration-dependent tuning of ERK signaling dynamics in migrating neutrophils.Science signaling · 2016Article
- The effects of corticosteroids on COPD lung macrophages: a pooled analysis.Respiratory research · 2015Article
- Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsSome asthma patients remain symptomatic despite using high doses of inhaled corticosteroids (ICS). We used alveolar macrophages to identify individual patients with insensitivity to corticosteroids and to evaluate the anti-inflammatory effects of a p38 mitogen-activated protein kinase (MAPK) inhibitor combined with a corticosteroid on these cells.
methodsAlveolar macrophages from 27 asthma patients (classified according to the Global Initiative for Asthma (GINA) treatment stage. Six GINA1, 10 GINA2 and 11 GINA3/4) were stimulated with lipoploysaccharide (LPS) (1 μg ml(-1)). The effects of dexamethasone (dex 1-1000 nm), the p38 MAPK inhibitor 1-(5-tert-butyl-2-p-tolyl-2Hpyrazol-3-yl)-3(4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl)urea (BIRB-796 1-1000 nm) and both drugs combined at all concentrations on supernatant TNFα, IL-6 and CXCL-8 concentrations were analyzed by ELISA. Dose-sparing and efficacy enhancing effects of combination treatment were determined.
resultsDexamethasone reduced LPS-induced TNFα, IL-6 and CXCL-8 in all groups, but maximum inhibition was significantly reduced for GINA3/4 compared with GINA2 and GINA1 (P < 0.01). A subgroup of corticosteroid insensitive patients with a reduced effect of dexamethasone on cytokine secretion were identified. BIRB-796 in combination with dexamethasone significantly increased cytokine inhibition compared with either drug alone (P < 0.001) in all groups. This effect was greater in corticosteroid insensitive compared with sensitive patients. There were significant synergistic dose-sparing effects (P < 0.05) for the combination treatment on inhibition of TNFα, IL-6 and CXCL-8 in all groups. There was also significant efficacy enhancing benefits (P < 0.05) on TNFα and IL-6.
conclusionsp38 MAPK inhibitors synergistically enhance efficacy of corticosteroids in macrophages from asthma patients. This effect is greater in corticosteroid insensitive asthma patients, suggesting that this class of drug should be targeted to this patient phenotype.
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