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706 results on '"Gilkeson, Gary S"'

206. In vitro evaluation of the effects of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) on IL-2 production in human T-cells.

Author

Midgett, Kristin, Peden‐Adams, Margie M., Gilkeson, Gary S., and Kamen, Diane L.

Subjects
PERFLUOROOCTANE sulfonate, PERFLUOROOCTANOIC acid, T cells, INTERLEUKIN-2, AUTOIMMUNE diseases, SYSTEMIC lupus erythematosus
Abstract

Perfluorinated compounds, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), have been shown to alter various immune functions suggesting they are immunotoxic. This study assessed the effects of PFOS and PFOA on interleukin (IL)-2 production in the human Jurkat T-cell line and PFOS in healthy human primary T cells. Jurkat cells were stimulated with phytohemagglutinin (PHA)/phorbol myristate acetate (PMA), anti CD-3/anti CD-28, or anti CD-3, and dosed with 0, 0.05, 0.1, 0.5, 1, 5, 10, 50, 75, or 100 µg ml−1 PFOS or 0, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 5, or 10 µg ml−1 PFOA. Jurkat cells stimulated with PHA/PMA or anti CD-3 exhibited decreased IL-2 production beginning at 50 µg PFOS ml−1 and 5 µg PFOS ml−1 respectively, but stimulation with anti-CD3/anti-CD28 resulted in no changes compared with the control. Addition of the PPAR-alpha antagonist GW6471 to PFOS-dosed cells stimulated with PHA/PMA resulted in decreases in IL-2 production starting at 50 µg PFOS ml−1, which suggests PFOS affected T-cell IL-2 production via PPAR-alpha-independent mechanisms. Exposure to PFOA, PFOA + GW6471, or PFOS + PFOA in Jurkat cells resulted in no significant differences in IL-2 production. In vitro dosing studies using healthy primary human CD4+ T cells were consistent with the Jurkat results. These data demonstrated that PFOA did not impact IL-2 production, but PFOS suppressed IL-2 production in both a human cell line and human primary cells at dose levels within the high end of the human exposure range. A decrease in IL-2 production is characteristic of autoimmune diseases such as systemic lupus erythematosus and should be further investigated. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2015
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216. Genetic polymorphisms in tumor necrosis factor (TNF)-α and TNF-β in a population-based study of systemic lupus erythematosus: associations and interaction with the interleukin-1α-889 C/T polymorphism

Author

Parks, Christine G, primary, Pandey, Janardan P, additional, Dooley, Mary Anne, additional, Treadwell, Edward L, additional, St. Clair, E.W, additional, Gilkeson, Gary S, additional, Feghali-Bostwick, Carol A, additional, and Cooper, Glinda S, additional

Published
2004
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226. Occupational exposure to crystalline silica and risk of systemic lupus erythematosus: A population-based, case-control study in the Southeastern United States

Author

Parks, Christine G., primary, Cooper, Glinda S., additional, Nylander-French, Leena A., additional, Sanderson, Wayne T., additional, Dement, John M., additional, Cohen, Philip L., additional, Dooley, Mary Anne, additional, Treadwell, Edward L., additional, St.Clair, E. William, additional, Gilkeson, Gary S., additional, Hoppin, Jane A., additional, and Savitz, David A., additional

Published
2002
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247. A Pathogenetic Role for TNFα in the Syndrome of Cachexia, Arthritis, and Autoimmunity Resulting from Tristetraprolin (TTP) Deficiency

Author

Taylor, Gregory A, primary, Carballo, Ester, additional, Lee, David M, additional, Lai, Wi S, additional, Thompson, Michael J, additional, Patel, Dhavalkumar D, additional, Schenkman, Daniel I, additional, Gilkeson, Gary S, additional, Broxmeyer, Hal E, additional, Haynes, Barton F, additional, and Blackshear, Perry J, additional

Published
1996
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250. MicroRNA-3148 Modulates Allelic Expression of Toll-Like Receptor 7 Variant Associated with Systemic Lupus Erythematosus.

Author

Yun Deng, Jian Zhao, Sakurai, Daisuke, Kaufman, Kenneth M., Edberg, Jeffrey C., Kimberly, Robert P., Kamen, Diane L., Gilkeson, Gary S., Jacob, Chaim O., Scofield, R. Hal, Langefeld, Carl D., Kelly, Jennifer A., Ramsey-Goldman, Rosalind, Petri, Michelle A., Reveille, John D., Vilá, Luis M., Alarcón, Graciela S., Vyse, Timothy J., Pons-Estel, Bernardo A., and Freedman, Barry I.

Subjects
MICRORNA, COMPLEMENTATION (Genetics), GENE expression, SYSTEMIC lupus erythematosus, GENETICS of autoimmune diseases, GENETICS
Abstract

We previously reported that the G allele of rs3853839 at 3' untranslated region (UTR) of Toll-like receptor 7 (TLR7) was associated with elevated transcript expression and increased risk for systemic lupus erythematosus (SLE) in 9,274 Eastern Asians [P = 6.5x10-10, odds ratio (OR) (95%CI) = 1.27 (1.17-1.36)]. Here, we conducted trans-ancestral fine-mapping in 13,339 subjects including European Americans, African Americans, and Amerindian/Hispanics and confirmed rs3853839 as the only variant within the TLR7-TLR8 region exhibiting consistent and independent association with SLE (Pmeta = 7.5x10-11, OR = 1.24 [1.18-1.34]). The risk G allele was associated with significantly increased levels of TLR7 mRNA and protein in peripheral blood mononuclear cells (PBMCs) and elevated luciferase activity of reporter gene in transfected cells. TLR7 39UTR sequence bearing the non-risk C allele of rs3853839 matches a predicted binding site of microRNA-3148 (miR-3148), suggesting that this microRNA may regulate TLR7 expression. Indeed, miR-3148 levels were inversely correlated with TLR7 transcript levels in PBMCs from SLE patients and controls (R² = 0.255, P = 0.001). Overexpression of miR-3148 in HEK-293 cells led to significant dose-dependent decrease in luciferase activity for construct driven by TLR7 39UTR segment bearing the C allele (P = 0.0003). Compared with the G-allele construct, the C-allele construct showed greater than two-fold reduction of luciferase activity in the presence of miR-3148. Reduced modulation by miR-3148 conferred slower degradation of the risk G-allele containing TLR7 transcripts, resulting in elevated levels of gene products. These data establish rs3853839 of TLR7 as a shared risk variant of SLE in 22,613 subjects of Asian, EA, AA, and Amerindian/Hispanic ancestries (Pmeta = 2.0x10-19, OR = 1.25 [1.20-1.32]), which confers allelic effect on transcript turnover via differential binding to the epigenetic factor miR-3148. [ABSTRACT FROM AUTHOR]

Published
2013
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