Regulatory effects of estriol on T cell migration and cytokine profile: inhibition of transcription factor NF-kappa B.
The protective role of pregnancy in autoimmune conditions, such as multiple sclerosis (MS), is potentially associated with immune regulation by sex hormones produced during pregnancy. This study was undertaken to examine the regulatory effects of estriol on the T cell functions, including transmigration and the cytokine production. The results revealed for the first time that estriol significantly inhibited T cell transmigration at a concentration range typical of pregnancy, which correlated with decreased T cell expression of matrix metalloproteinase-9. Estriol was also found to alter the cytokine profile of T cells toward Th2 phenotype by up-regulating the production of IL-10 and inhibiting TNFalpha secretion of T cells. However, the inhibitory effects of estriol on T cells were not antigen-dependent. Further characterization indicated that estriol inhibited nuclear transcription factor kappa B (NF-kappa B), which controls a variety of immune-related genes. This study provides new evidence that estriol is a potent regulator for the T cell functions potentially through its interaction with the NF-kappa B signaling pathway.
Zang
Ying C Q
YC
Multiple Sclerosis Research Unit, Baylor-Methodist Multiple Sclerosis Center and Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Halder
Jyotsnabaran B
JB
Hong
Jian
J
Rivera
Victor M
VM
Zhang
Jingwu Z
JZ
D000328:Adult; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000097:blood*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004964:Estriol / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D020780:Matrix Metalloproteinase 9; D004964:Estriol