Estradiol targets T cell signaling pathways in human systemic lupus.
The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol) were measured by real time polymerase chain amplification. Estradiol uniquely upregulated six pathways in SLE T cells that control T cell function including interferon-alpha signaling. Measurement of interferon-alpha pathway target gene expression revealed significant differences (p= 0.043) in DRIP150 (+/- estradiol) in SLE T cell samples while IFIT1 expression was bimodal and correlated moderately (r= 0.55) with disease activity. The results indicate that estradiol alters signaling pathways in activated SLE T cells that control T cell function. Differential expression of transcriptional coactivators could influence estrogen-dependent gene regulation in T cell signaling and contribute to SLE onset and disease pathogenesis.
Department of Biology, Pittsburg State University, Pittsburg, KS 66762, USA.
Emily
E
Walters
Virginia
V
Rider
Nabih I
NI
Abdou
Cindy
C
Greenwell
Stan
S
Svojanovsky
Peter
P
Smith
Bruce F
BF
Kimler
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D056892:Mediator Complex / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C484290:IFIT1 protein, human; C492160:MED14 protein, human; D056892:Mediator Complex; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D004958:Estradiol