[Dose-response effect of steroid hormones on the Gfi1 and U2afil4 gene expression in T lymphocytes at different stages of differentiation].
Alternative splicing of Ptprc gene is a key event in memory T cell differentiation. This gene encodes transmembrane tyrosine phosphatase CD45. One of potential mechanisms of alternative splicing regulation is based on antagonistic effects of auxiliary splicing factor U2AF26 and transcription factor Gfi1. These two proteins regulate antigen-dependent T cell activation. We have shown that steroid hormones have different effects on U2af1l4 and Gfi1 transcription regulation in dissimilar differentiation stage cell culture, subjected to antigen-independent stimulation. Low concentrations of glucocorticoid (Dex) and female sex hormone (Est) can activate expression of U2af1l4 in re-stimulated cells that probably induce terminal receptor CD45 isoforms formation mechanism, whereas high doses of hormones inhibit the process. In the same conditions Dex in a wide range of concentrations (10(-5)-10(-7) M) and Est (10(-6) and 10(-7) M) activate U2af1l4 gene expression that probably leads to "surrogate memory T cells" formation. Dose dependent testosterone (Test) effect is opposite to Est and Dex effect on priming (CD45RO+) and naive (CD45RA+) lymphocytes. The role of steroid hormones in memory T cell differentiation in antigen-independent stimulation conditions is of great interest for the understanding of chronic hormonal and immune disbalance mechanisms.
L S
LS
Litvinova
I O
IO
Mazunin
A A
AA
Gutsol
N A
NA
Sokhonevich
O G
OG
Khaziakhmatova
K A
KA
Kofanova
D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017493:Leukocyte Common Antigens / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D000072668:Splicing Factor U2AF; D013256:Steroids / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; D013256:Steroids; D014157:Transcription Factors; C486290:U2AF1L4 protein, human; D004958:Estradiol; D003907:Dexamethasone; D017493:Leukocyte Common Antigens