Abstract
Lung fibroblasts are involved in airway inflammation and remodelling in COPD. We report an investigation of the effects of combining a p38 MAPK inhibitor with a corticosteroid on cytokine production by a human lung fibroblast cell line and primary fibroblasts obtained from human lung tissue. Our main interest was to determine whether additive or synergistic anti‐inflammatory effects would be observed. We observed inhibition of IL‐6 and CXCL8 secretion from both lung fibroblast models by dexamethasone (maximal inhibition 40–90%) and the p38 MAPK inhibitor BIRB (maximal inhibition 30–60%), used alone and evidence of increased anti‐inflammatory effects when used in combination. This combination effect was more apparent for TNF‐a stimulated cytokine production (maximal inhibition increased by 10–20%). Interaction ratio analysis showed this enhanced effect to be additive rather than synergistic interaction. Similar results were obtained using both fibroblast cell culture models. Combining a p38 MAPK to corticosteroids may help reduce fibroblast mediated inflammation in COPD.
Highlights
Fibroblasts are involved in airway remodelling in chronic obstructive pulmonary disease (COPD) [1]
Fibroblasts from COPD patients secrete higher levels of interleukin-6 (IL-6) and C-X-C motif chemokine ligand 8 (CXCL8) compared to healthy controls [3], which may contribute to the persistent inflammation in COPD lungs
This paper reports an investigation of the effects of combining a p38 mitogen-activated protein kinase (MAPK) inhibitor with a corticosteroid on cytokine production by pulmonary fibroblasts
Summary
Fibroblasts are involved in airway remodelling in chronic obstructive pulmonary disease (COPD) [1]. These cells regulate the structure of the extracellular matrix (ECM) by secreting collagens, elastins and matrix metalloproteinases, which contribute to ECM turnover [2]. Fibroblasts from COPD patients secrete higher levels of interleukin-6 (IL-6) and C-X-C motif chemokine ligand 8 (CXCL8) compared to healthy controls [3], which may contribute to the persistent inflammation in COPD lungs. Inhaled corticosteroids (ICS) are commonly used anti-inflammatory drugs in COPD. Many COPD patients using ICS have persistent airway inflammation [5,6] and continue to suffer with a heavy burden of symptoms and exacerbations [7]
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