Source:http://linkedlifedata.com/resource/pubmed/id/11600182
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-2
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pubmed:dateCreated |
2001-10-15
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pubmed:abstractText |
Gamma-interferon (IFN-gamma) plays an important role in the maintenance of immune homeostasis by regulating the functions of all key cells of the immune system. Pathologically, IFN-gamma has been implicated in several autoimmune diseases. Since estrogens affect autoimmunity, we investigated whether immunomodulatory estrogenic hormones affects IFN-gamma. Concanavalin-A-stimulated splenic lymphocytes from orchiectomized or ovariectomized C57BL/6 mice exposed to estrogen for 3-5 months secreted higher levels of IFN-gamma protein compared to controls. This increase is, in part, due to increased levels of IFN-gamma mRNA. Kinetic studies suggested that splenic lymphocytes from estrogen-treated gonadectomized mice had increased IFN-gamma mRNA and protein as early as 6-12 h of culture. Estrogen also increased the expression of co-stimulatory CD80 (B7-1) molecules on B cells. Since natural estrogen increases IFN-gamma, it became important to test whether diethylstilbestrol (DES, a synthetic estrogen which was given to millions of women) also alters IFN-gamma levels. Our initial investigatory studies show that prenatal mice exposed to DES had a normal ability to secrete IFN-gamma. However, a second exposure of these mice to DES (single dose of 1 microg/g.b.w), as late as 1-1.5 years of age, led to a pronounced increase in the number of IFN-gamma secreting cells and augmented secretion of IFN-gamma. Increased IFN-gamma secretion by splenic lymphocytes from these mice was noted even after stimulation with a submitogenic concentration of anti-CD3 antibodies with or without anti-CD28 antibodies. Cell mixing experiments suggested that the DES-induced increase in IFN-gamma secretion is due to hormonal effects on T cells but not on APC. Together our studies show that: (1) estrogens upregulate IFN-gamma secretion, a vital immunoregulatory cytokine, and (2) inappropriate exposure of developing fetus to DES may permanently alter the "cytokine programming" of lymphocytes.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Diethylstilbestrol,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogens, Non-Steroidal,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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pubmed:status |
MEDLINE
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pubmed:issn |
0165-0378
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
113-27
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11600182-Animals,
pubmed-meshheading:11600182-Cells, Cultured,
pubmed-meshheading:11600182-Diethylstilbestrol,
pubmed-meshheading:11600182-Estradiol,
pubmed-meshheading:11600182-Estrogens, Non-Steroidal,
pubmed-meshheading:11600182-Female,
pubmed-meshheading:11600182-Interferon-gamma,
pubmed-meshheading:11600182-Lymphocytes,
pubmed-meshheading:11600182-Male,
pubmed-meshheading:11600182-Mice,
pubmed-meshheading:11600182-Mice, Inbred C57BL,
pubmed-meshheading:11600182-Orchiectomy,
pubmed-meshheading:11600182-Ovariectomy,
pubmed-meshheading:11600182-RNA, Messenger,
pubmed-meshheading:11600182-Spleen,
pubmed-meshheading:11600182-T-Lymphocytes,
pubmed-meshheading:11600182-Up-Regulation
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pubmed:articleTitle |
Interferon-gamma levels are upregulated by 17-beta-estradiol and diethylstilbestrol.
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pubmed:affiliation |
Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, VA 24060-0342, USA. ansrahmd@vt.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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