Cortisol is a potent modulator of lipopolysaccharide-induced interferon signaling in macrophages.
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.
Billing
Anja M
AM
Institute of Immunology, CRP-Santé/National Public Health Laboratory, 20A rue Auguste Lumiére, Luxembourg, Grand Duchy of Luxembourg.
Fack
Fred
F
Turner
Jonathan D
JD
Muller
Claude P
CP
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D004357:Drug Synergism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D040901:Proteomics; D015398:Signal Transduction / Q000187:drug effects; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
D000893:Anti-Inflammatory Agents; D006854:Hydrocortisone; D050838:Interferon Regulatory Factor-3; D007371:Interferon-gamma; D008070:Lipopolysaccharides; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C494232:IRF3 protein, human