Phospho-p38 MAPK expression in COPD patients and asthmatics and in challenged bronchial epithelium

Davide Vallese, Fabio L M Ricciardolo, Isabella Gnemmi, Paolo Casolari, Paola Brun, Valentina Sorbello, Armando Capelli, Francesco Cappello, Giorgio Narciso Cavallesco, Alberto Papi, Kian Fan Chung, Bruno Balbi, Ian M. Adcock, Gaetano Caramori, Antonino Di Stefano

Research output: Contribution to journalArticle

Abstract

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 (H2O2), 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 H2O2 and LPS treatment. JNK1 and ERK1 mRNA were unchanged after H2O2, 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.

Original languageEnglish
Pages (from-to)329-342
Number of pages14
JournalRespiration
Volume89
Issue number4
DOIs
Publication statusPublished - Apr 21 2015

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Keywords

  • Asthma phenotypes
  • Chronic obstructive pulmonary disease phenotypes
  • Mitogen-activated protein kinases
  • p65
  • Pathology of chronic obstructive pulmonary disease

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Medicine(all)

Cite this

Vallese, D., Ricciardolo, F. L. M., Gnemmi, I., Casolari, P., Brun, P., Sorbello, V., Capelli, A., Cappello, F., Cavallesco, G. N., Papi, A., Chung, K. F., Balbi, B., Adcock, I. M., Caramori, G., & Di Stefano, A. (2015). Phospho-p38 MAPK expression in COPD patients and asthmatics and in challenged bronchial epithelium. Respiration, 89(4), 329-342. https://doi.org/10.1159/000375168