Cortisol is a potent modulator of lipopolysaccharide-induced interferon signaling in macrophages

Anja Billing, Fred Fack, Jonathan D. Turner, Claude P. Muller

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The effects of cortisol (CORT) on resting and lipopolysaccharide (LPS)-activated monocyte-derived THP-1 macrophages were investigated by proteomics. Forty-seven proteins were found to be modulated, 20 by CORT, 11 by LPS, and 16 by CORT and LPS. Cortisol-sensitive chaperones and cytoskeletal proteins were mostly repressed. HCLS1, MGN, and MX1 were new proteins identified to be under the transcriptional control of this steroid and new CORT-sensitive variants of MX1, SYWC and IFIT3 were found. FKBP51, a known CORT target gene, showed the strongest response to CORT and synergism with LPS. In resting THP-1 macrophages, 18 proteins were modulated by CORT, with 15 being down-regulated. Activation of macrophages by LPS was associated with enhanced expression of immune response and metabolic proteins. In activated macrophages, CORT had a more equilibrated effect and almost all metabolism-related proteins were up-regulated, whereas immune response proteins were mostly down-regulated. The majority of the LPS up-regulated immune response-related proteins are known interferon (IFN) target genes (IFIT3, MX1, SYWC, PSME2) suggesting activation of the IRF3 signaling pathway. They were all suppressed by CORT. This is the first proteomics study to investigate the effects of CORT on activated immune cells.

Original languageEnglish
Pages (from-to)302-320
Number of pages19
JournalInnate Immunity
Volume17
Issue number3
DOIs
Publication statusPublished - 1 Jun 2011
Externally publishedYes

Fingerprint

Interferons
Lipopolysaccharides
Hydrocortisone
Macrophages
Proteins
Proteomics
Cytoskeletal Proteins
Macrophage Activation
Genes
Monocytes
Steroids

Keywords

  • 2-D DIGE
  • cortisol
  • FKBP51
  • IRF3
  • LPS
  • MX1

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

Cite this

Cortisol is a potent modulator of lipopolysaccharide-induced interferon signaling in macrophages. / Billing, Anja; Fack, Fred; Turner, Jonathan D.; Muller, Claude P.

In: Innate Immunity, Vol. 17, No. 3, 01.06.2011, p. 302-320.

Research output: Contribution to journalArticle

Billing, Anja ; Fack, Fred ; Turner, Jonathan D. ; Muller, Claude P. / Cortisol is a potent modulator of lipopolysaccharide-induced interferon signaling in macrophages. In: Innate Immunity. 2011 ; Vol. 17, No. 3. pp. 302-320.
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