Phospho-p38 MAPK Expression in COPD Patients and Asthmatics and in Challenged Bronchial Epithelium

• Published in: Respiration Vol. 89; no. 4; pp. 329 - 342
• Main Authors: Vallese, Davide, Ricciardolo, Fabio L.M., Gnemmi, Isabella, Casolari, Paolo, Brun, Paola, Sorbello, Valentina, Capelli, Armando, Cappello, Francesco, Cavallesco, Giorgio Narciso, Papi, Alberto, Chung, Kian Fan, Balbi, Bruno, Adcock, Ian M., Caramori, Gaetano, Di Stefano, Antonino
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2015
• Subjects: Aged; Asthma; Asthma - enzymology; Basic Science Investigations; Blotting, Western; Bronchi - enzymology; Bronchi - immunology; Case-Control Studies; Cell Line; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Comparative analysis; Diagnosis; Epithelium; Female; Gene expression; Genetic aspects; Health aspects; Humans; Immunohistochemistry; Interleukin-8 - metabolism; Kinases; Lung research; Lymphocyte Count; Male; Middle Aged; Mitogen-activated protein kinases; p38 Mitogen-Activated Protein Kinases - metabolism; Pulmonary Disease, Chronic Obstructive - enzymology; Respiratory Mucosa - enzymology; Respiratory Mucosa - immunology; Transcription Factor RelA - metabolism; United Kingdom; Pathology of chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease phenotypes; Asthma phenotypes; p65; Mitogen-activated protein kinases
• ISSN: 0025-7931; 1423-0356; 1423-0356
• DOI: 10.1159/000375168

Background: The role of mitogen-activated protein kinases (MAPK) in regulating the inflammatory response in the airways of patients with chronic obstructive pulmonary disease (COPD) and asthmatic patients is unclear. Objectives: To investigate the expression of activated MAPK in lungs of COPD patients and in bronchial biopsies of asthmatic patients and to study MAPK expression in bronchial epithelial cells in response to oxidative and inflammatory stimuli. Methods: Immunohistochemical expression of phospho (p)-p38 MAPK, p-JNK1 and p-ERK1/2 was measured in bronchial mucosa in patients with mild/moderate (n = 17), severe/very severe (n = 16) stable COPD, control smokers (n = 16), control non-smokers (n = 9), in mild asthma (n = 9) and in peripheral airways from COPD patients (n = 15) and control smokers (n = 15). Interleukin (IL)-8 and MAPK mRNA was measured in stimulated 16HBE cells. Results: No significant differences in p-p38 MAPK, p-JNK or p-ERK1/2 expression were seen in bronchial biopsies and peripheral airways between COPD and control subjects. Asthmatics showed increased submucosal p-p38 MAPK expression compared to COPD patients (p < 0.003) and control non-smokers (p < 0.05). Hydrogen peroxide (H 2 O 2 ), cytomix (tumour necrosis factor-α + IL-1β + interferon-γ) and lipopolysaccharide (LPS) upregulated IL-8 mRNA at 1 or 2 h. p38 MAPKα mRNA was significantly increased after H 2 O 2 and LPS treatment. JNK1 and ERK1 mRNA were unchanged after H 2 O 2 , cytomix or LPS treatments. Conclusion: p-p38 MAPK expression is similar in stable COPD and control subjects but increased in the bronchi of mild asthmatics compared to stable COPD patients. p38 MAPK mRNA is increased after bronchial epithelial challenges in vitro. These data together suggest a potential role for this MAPK in Th2 inflammation and possibly during COPD exacerbations.