Proteomic analysis of the cortisol-mediated stress response in THP-1 monocytes using DIGE technology

Anja M. Billing, Fred Fack, Jenny Renaut, Christophe M. Olinger, Andrea B. Schote, Jonathan D. Turner, Claude P. Muller

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Abstract

The glucocorticoid (GC) cortisol, the main mediator of the hypothalamic-pituitary-adrenal axis has many implications in metabolism, stress response and the immune system. Its function is mediated via binding to the glucocorticoid receptor (GR), a member of the superfamily of ligand-activated nuclear hormone receptors. The activity of the ligated GR results from its binding as a transcription factor to glucocorticoid response elements (GREs). Two-dimensional gel electrophoresis with DIGE (fluorescence difference gel electrophoresis) technology was applied to study the effects of cortisol on the human THP-1 monocytic cell line. A total of 28 cortisol-modulated proteins were identified belonging to five functional groups: cytoskeleton (8), chaperones (9), immune response (4), metabolism (3) and transcription/translation (4). Their corresponding genes were screened for putative GREs in their +10 kb/-0.2 kb promoter regions including all alternative promoters available within the Database for Transcription Start Sites (DBTSS). FKBP51, known to be induced by cortisol, was identified as the strongest differentially expressed protein, and contains the highest number of strict GREs. Genomic analysis of five alternative FKBP5 promoter regions suggests GC inducibility of all transcripts. Additionally, proteomics (2D DIGE and 2D immunoblotting) revealed the existence of several FKBP51 isoforms, which were not previously described. To our knowledge this is the first proteomic study that addresses the effects of cortisol on immune cells. FKBP51 isoforms found on the gel map were linked to alternative promoter usage on the genetic level, successfully correlating both the specific proteomic and genomic findings.

Original languageEnglish
Pages (from-to)1433-1444
Number of pages12
JournalJournal of Mass Spectrometry
Volume42
Issue number11
DOIs
Publication statusPublished - 1 Nov 2007

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Keywords

  • 2D DIGE
  • Alternative promoters
  • Cortisol
  • FKBP51
  • Glucocorticoid receptor
  • Glucocorticoid response element

ASJC Scopus subject areas

  • Spectroscopy

Cite this

Billing, A. M., Fack, F., Renaut, J., Olinger, C. M., Schote, A. B., Turner, J. D., & Muller, C. P. (2007). Proteomic analysis of the cortisol-mediated stress response in THP-1 monocytes using DIGE technology. Journal of Mass Spectrometry, 42(11), 1433-1444. https://doi.org/10.1002/jms.1270