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Your search keyword '"Stellato, Cristiana"' showing total 15 results
Start Over Author "Stellato, Cristiana" Publisher the american association of immunologists
15 results on '"Stellato, Cristiana"'

3. The RNA-binding protein HuR coordinately regulates GATA-3 and Th2 cytokine gene expression in dose dependent manner (P6262)

Author

Ulus, Atasoy, Matthew, Gubin, Robert, Calaluce, Joseph, Magee, Jennifer, Martindale, Myriam, Gorospe, Casolaro, Vincenzo, and Stellato, Cristiana

Subjects
Immunology, Immunology and Allergy
Abstract

Posttranscriptional control by RNA binding proteins (RBPs) is poorly understood. Th2 mediated diseases such as asthma, are driven by GATA-3, IL-4 and IL-13. The RBP, HuR, regulates IL-4 and IL-13 by increasing mRNA stability. We identified GATA-3, IL-4 and IL-13 as HuR targets and hypothesized HuR may be coordinately regulating Th2 differentiation by controlling mRNA stability and translatability. We made a HuR CD4+T transgenic mouse, and a HuR conditional knock out mouse (HuRfl/fl) to ablate HuR in T cells. HuR over-expression in transgenic CD4+ T cells stabilized GATA-3, IL-4 and IL-13 mRNAs, and increased mRNA, protein and Th2 polarization. HuR knock-down resulted in decreases in GATA-3, IL-4 and IL-13 expression. Findings were confirmed in human naïve and memory T cells. We defined HuR binding sites in GATA-3. Th2 cells with low HuR levels (26%) from HuRfl/+ mice, had decreases in IL-4, IL-13 and GATA-3 mRNA but not protein. Surprisingly, CD4+ T cells from HuRfl/fl mice (93% knockdown) showed increased IL-2, IL-4, IL-13 mRNA and protein. IL-4 transcription increased but mRNA stability remained unchanged. IL-2 and IL-13 transcription were unaltered but there were increases in mRNA stability. Polysomal gradient analysis revealed similar translation. We analyzed gene expression in KO vs. control CD4+ T cells to determine HuR targets. Ova challenge model of asthma corroborated ex vivo results. These data suggest HuR levels regulate Th2 cytokines and Th2 differentiation.

Published
2013
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4. Coordinate Regulation of GATA-3 and Th2 Cytokine Gene Expression by the RNA-Binding Protein HuR

Author

Stellato, Cristiana, primary, Gubin, Matthew M., additional, Magee, Joseph D., additional, Fang, Xi, additional, Fan, Jinshui, additional, Tartar, Danielle M., additional, Chen, Jing, additional, Dahm, Garrett M., additional, Calaluce, Robert, additional, Mori, Francesca, additional, Jackson, Glenn A., additional, Casolaro, Vincenzo, additional, Franklin, Craig L., additional, and Atasoy, Ulus, additional

Published
2011
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12. Cutaneous Injection of Human Subjects with Macrophage Inflammatory Protein-1α Induces Significant Recruitment of Neutrophils and Monocytes

Author

Lee, Sang Chin, primary, Brummet, Mary E., additional, Shahabuddin, Syed, additional, Woodworth, Thasia G., additional, Georas, Steve N., additional, Leiferman, Kristin M., additional, Gilman, Steven C., additional, Stellato, Cristiana, additional, Gladue, Ron P., additional, Schleimer, Robert P., additional, and Beck, Lisa A., additional

Published
2000
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15. Role of the RNA-Binding Protein Tristetraprolin in Glucocorticoid-Mediated Gene Regulation

Author

Cristiana Stellato, William F. C. Rigby, Myriam Gorospe, Ulus Atasoy, Maria Rosaria Galdiero, Xi Fang, Faoud T. Ishmael, Chris Cheadle, Ishmael, Faoud T, Fang, Xi, Galdiero, Maria Rosaria, Atasoy, Ulu, Rigby, William F C, Gorospe, Myriam, Cheadle, Chri, and Stellato, Cristiana

Subjects
Small interfering RNA, RNA Stability, Immunology, Tristetraprolin, RNA-binding protein, RNA-Binding Protein, Biology, Article, Cell Line, Proinflammatory cytokine, Mice, Glucocorticoid, Embryonic Stem Cell, hemic and lymphatic diseases, Gene expression, Animals, Humans, Immunology and Allergy, Gene silencing, heterocyclic compounds, Gene Silencing, Budesonide, Glucocorticoids, Cells, Cultured, Embryonic Stem Cells, Oligonucleotide Array Sequence Analysis, Mice, Knockout, Regulation of gene expression, Animal, Oligonucleotide Array Sequence Analysi, Gene Expression Profiling, RNA-Binding Proteins, Fibroblasts, respiratory system, Molecular biology, Up-Regulation, Gene expression profiling, Gene Expression Regulation, Fibroblast, therapeutics, Human
Abstract

Glucocorticoids (GCs) are the mainstay of anti-inflammatory therapy. Modulation of posttranscriptional regulation (PTR) of gene expression by GCs is a relevant yet poorly characterized mechanism of their action. The RNA-binding protein tristetraprolin (TTP) plays a central role in PTR by binding to AU-rich elements in the 3′-untranslated region of proinflammatory transcripts and accelerating their decay. We found that GCs induce TTP expression in primary and immortalized human bronchial epithelial cells. To investigate the importance of PTR and the role of TTP in GC function, we compared the effect of GC treatment on genome-wide gene expression using mouse embryonic fibroblasts (MEFs) obtained from wild-type and TTP−/− mice. We confirmed that GCs induce TTP in MEFs and observed in TTP−/− MEFs a striking loss of up to 85% of GC-mediated gene expression. Gene regulation by TNF-α was similarly affected, as was the antagonistic effect of GC on TNF-α-induced response. Inflammatory genes, including cytokines and chemokines, were among the genes whose sensitivity to GCs was affected by lack of TTP. Silencing of TTP in WT MEFs by small interfering RNA confirmed loss of GC response in selected targets. Immunoprecipitation of ribonucleoprotein complexes revealed binding of TTP to several validated transcripts. Changes in the rate of transcript degradation studied by actinomycin D were documented for only a subset of transcripts bound to TTP. These results reveal a strong and previously unrecognized contribution of PTR to the anti-inflammatory action of GCs and point at TTP as a key factor mediating this process through a complex mechanism of action.

Published
2008
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