High ICAM-1 gene expression in pulmonary fibroblasts of COPD patients: a reflection of an enhanced immunological function

A. Zandvoort, Y. M. van der Geld, M. R. Jonker, J. A. Noordhoek, J. T. W. M. Vos, J. Wesseling, H. F. Kauffman, W. Timens*, D. S. Postma

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)

Abstract

Chronic obstructive pulmonary disease (COPD) is characterised by destruction of extracellular matrix (ECM) in parenchymal areas, whereas the bronchial walls can show fibrosis. In addition, an extensive inflammatory process is observed. CD8+ T-cells, located throughout the lung, and epithelial cells in centrally located airways, produce cytokines involved in the inflammatory process. These cytokines may influence the present fibroblasts, the key effectors in the defective ECM repair and maintenance in COPD.

The current authors explored the effects of the cytokine microenvironment on cell-cell interaction gene expression in pulmonary fibroblasts of controls (n=6), and Global Initiative for Chronic Obstructive Lung Disease stage II (n=7) and stage IV (n=7) COPD patients. The current authors simulated the in vivo microenvironment using supernatants of CD3/CD28 stimulated CD8+ T-cells isolated from peripheral blood of COPD patients, supernatant of a bronchial-epithelial cell line, or a combination of both.

The present data show that fibroblasts of chronic obstructive pulmonary disease patients display an altered response to the cytokine microenvironment, depending on both the disease stage and the central or peripheral location in the lung. Especially adhesion-related genes are upregulated in fibroblasts of chronic obstructive pulmonary disease patients, which can indicate a more pronounced role of fibroblasts in the inflammatory process in chronic obstructive pulmonary disease, possibly resulting in reduced function as effectors of extracellular matrix repair.

Original languageEnglish
Pages (from-to)113-122
Number of pages10
JournalEuropean Respiratory Journal
Volume28
Issue number1
DOIs
Publication statusPublished - Jul-2006

Keywords

  • CD8+T-cells
  • chronic inflammation
  • chronic obstructive pulmonary disease
  • intracellular adhesion molecule-1
  • lung fibroblasts
  • INTERCELLULAR-ADHESION MOLECULE-1
  • HUMAN LUNG FIBROBLASTS
  • MICROARRAY DATA
  • EXTRACELLULAR-MATRIX
  • TNF-ALPHA
  • DISEASE
  • CLASSIFICATION
  • TRANSFORMATION
  • PATHOGENESIS
  • INFLAMMATION

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