DNA microarray analysis of gene expression in alveolar epithelial cells in response to TNFα, LPS, and cyclic stretch

C. C. Dos Santos, B. Han, C. F. Andrade, X. Bai, S. Uhlig, R. Hubmayr, M. Tsang, M. Lodyga, S. Keshavjee, A. S. Slutsky, M. Liu

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Recent evidence suggests that alveolar epithelial cells (AECs) may contribute to the development, propagation, and resolution of acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS). Proinflammatory cytokines, pathogen products, and injurious mechanical ventilation are important contributors of excessive inflammatory responses in the lung. In the present study, we used cDNA microarrays to define the gene expression patterns of A549 cells (an AEC line) in the early stages of three models of pulmonary parenchymal cell activation: cells treated with tumor necrosis factor-α (TNFα) (20 ng/ml), lipopolysaccharide (LPS, 1 μg/ml), or cyclic stretch (20% elongation) for either 1 h or 4 h. Differential gene expression profiles were determined by gene array analysis. TNFα induced an inflammatory response pattern, including induction of genes for chemokines, inflammatory mediators, and cell surface membrane proteins. TNFα also increased genes related to pro- and anti-apoptotic proteins, signal transduction proteins, and transcriptional factors. TNFα further induced a group of genes that may form a negative feedback loop to silence the NFκB pathway. Stimulation of AECs with mechanical stretch changed cell morphology and activated Src protein tyrosine kinase. The combination of TNFα plus stretch enhanced or attenuated expression of multiple genes. LPS decreased microfilament polymerization but had less impact on NFκB translocation and gene expression. Results from this study indicate that AECs can tailor their response to different stimuli or/and combination of stimuli and subsequently play an important role in acute inflammatory responses in the lung.

Original languageEnglish (US)
Pages (from-to)331-342
Number of pages12
JournalPhysiological Genomics
Volume19
DOIs
StatePublished - Jan 2005

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Alveolar Epithelial Cells
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Tumor Necrosis Factor-alpha
Gene Expression
Lung
Genes
Membrane Proteins
Apoptosis Regulatory Proteins
src-Family Kinases
Acute Lung Injury
Adult Respiratory Distress Syndrome
Actin Cytoskeleton
Transcriptome
Chemokines
Artificial Respiration
Polymerization
Lipopolysaccharides
Signal Transduction
Cytokines

Keywords

  • Acute lung injury
  • Acute respiratory distress syndrome
  • Mechanotransduction
  • Significant analysis of microarray
  • Ventilator-induced lung injury

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

DNA microarray analysis of gene expression in alveolar epithelial cells in response to TNFα, LPS, and cyclic stretch. / Dos Santos, C. C.; Han, B.; Andrade, C. F.; Bai, X.; Uhlig, S.; Hubmayr, R.; Tsang, M.; Lodyga, M.; Keshavjee, S.; Slutsky, A. S.; Liu, M.

In: Physiological Genomics, Vol. 19, 01.2005, p. 331-342.

Research output: Contribution to journalArticle

Dos Santos, CC, Han, B, Andrade, CF, Bai, X, Uhlig, S, Hubmayr, R, Tsang, M, Lodyga, M, Keshavjee, S, Slutsky, AS & Liu, M 2005, 'DNA microarray analysis of gene expression in alveolar epithelial cells in response to TNFα, LPS, and cyclic stretch', Physiological Genomics, vol. 19, pp. 331-342. https://doi.org/10.1152/physiolgenomics.00153.2004
Dos Santos, C. C. ; Han, B. ; Andrade, C. F. ; Bai, X. ; Uhlig, S. ; Hubmayr, R. ; Tsang, M. ; Lodyga, M. ; Keshavjee, S. ; Slutsky, A. S. ; Liu, M. / DNA microarray analysis of gene expression in alveolar epithelial cells in response to TNFα, LPS, and cyclic stretch. In: Physiological Genomics. 2005 ; Vol. 19. pp. 331-342.
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