Omeprazole Blocks STAT6 Binding to the Eotaxin-3 Promoter in Eosinophilic Esophagitis Cells
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{"title"=>"Omeprazole Blocks STAT6 Binding to the Eotaxin-3 Promoter in Eosinophilic Esophagitis Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Xi", "last_name"=>"Zhang", "scopus_author_id"=>"8252766200"}, {"first_name"=>"Edaire", "last_name"=>"Cheng", "scopus_author_id"=>"37160970100"}, {"first_name"=>"Xiaofang", "last_name"=>"Huo", "scopus_author_id"=>"35208660800"}, {"first_name"=>"Chunhua", "last_name"=>"Yu", "scopus_author_id"=>"37162376100"}, {"first_name"=>"Qiuyang", "last_name"=>"Zhang", "scopus_author_id"=>"37162406000"}, {"first_name"=>"Thai H.", "last_name"=>"Pham", "scopus_author_id"=>"55426323600"}, {"first_name"=>"David H.", "last_name"=>"Wang", "scopus_author_id"=>"55532142500"}, {"first_name"=>"Stuart J.", "last_name"=>"Spechler", "scopus_author_id"=>"35482365100"}, {"first_name"=>"Rhonda F.", "last_name"=>"Souza", "scopus_author_id"=>"7102113699"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84869853129", "sgr"=>"84869853129", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0050037", "pmid"=>"23185525", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"366113378"}, "id"=>"7821bdf8-c04a-3ae0-80f3-c91477131171", "abstract"=>"BACKGROUND: Patients who have esophageal eosinophilia without gastroesophageal reflux disease (GERD) nevertheless can respond to proton pump inhibitors (PPIs), which can have anti-inflammatory actions independent of effects on gastric acid secretion. In esophageal cell cultures, omeprazole has been reported to inhibit Th2 cytokine-stimulated expression of eotaxin-3, an eosinophil chemoattractant contributing to esophageal eosinophilia in eosinophilic esophagitis (EoE). The objective of this study was to elucidate molecular mechanisms underlying PPI inhibition of IL-4-stimulated eotaxin-3 production by esophageal cells.\\n\\nMETHODS/FINDINGS: Telomerase-immortalized and primary cultures of esophageal squamous cells from EoE patients were treated with IL-4 in the presence or absence of acid-activated omeprazole or lansoprazole. We measured eotaxin-3 protein secretion by ELISA, mRNA expression by PCR, STAT6 phosphorylation and nuclear translocation by Western blotting, eotaxin-3 promoter activation by an exogenous reporter construct, and STAT6, RNA polymerase II, and trimethylated H3K4 binding to the endogenous eotaxin-3 promoter by ChIP assay. Omeprazole in concentrations ≥5 µM significantly decreased IL-4-stimulated eotaxin-3 protein secretion and mRNA expression. Lansoprazole also blocked eotaxin-3 protein secretion. Omeprazole had no effect on eotaxin-3 mRNA stability or on STAT6 phosphorylation and STAT6 nuclear translocation. Rather, omeprazole blocked binding of IL-4-stimulated STAT6, RNA polymerase II, and trimethylated H3K4 to the eotaxin-3 promoter.\\n\\nCONCLUSIONS/SIGNIFICANCE: PPIs, in concentrations achieved in blood with conventional dosing, significantly inhibit IL-4-stimulated eotaxin-3 expression in EoE esophageal cells and block STAT6 binding to the promoter. These findings elucidate molecular mechanisms whereby patients with Th2 cytokine-driven esophageal eosinophilia can respond to PPIs, independent of effects on gastric acid secretion.", "link"=>"http://www.mendeley.com/research/omeprazole-blocks-stat6-binding-eotaxin3-promoter-eosinophilic-esophagitis-cells", "reader_count"=>35, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>5, "Student > Doctoral Student"=>3, "Researcher"=>10, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>3, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>5, "Student > Doctoral Student"=>3, "Researcher"=>10, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>3, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>22, "Agricultural and Biological Sciences"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>22}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Spain"=>2}, "group_count"=>2}

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/538426"], "description"=>"<p>Depicted is of one of at least 2 separate experiments. **, p≤0.01 compared to IL-4 stimulation alone; ***, p≤0.001 compared to IL-4 stimulation alone. C, unstimulated control cells.</p>", "links"=>[], "tags"=>["decreases", "il-4-stimulated", "eotaxin-3", "mrna", "levels", "eoe1-t", "eoe2-t", "lines", "pcr", "quantitative", "Real-time"], "article_id"=>208903, "categories"=>["Molecular Biology", "Biochemistry", "Chemistry", "Cell Biology"], "users"=>["Xi Zhang", "Edaire Cheng", "Xiaofang Huo", "Chunhua Yu", "Qiuyang Zhang", "Thai H. Pham", "David H. Wang", "Stuart J. Spechler", "Rhonda F. Souza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050037.g004", "stats"=>{"downloads"=>2, "page_views"=>101, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Omeprazole_Ome_decreases_IL_4_stimulated_eotaxin_3_mRNA_expression_levels_in_A_EoE1_T_and_B_EoE2_T_cell_lines_as_determined_by_conventional_PCR_and_quantitative_real_time_PCR_/208903", "title"=>"Omeprazole (Ome) decreases IL-4-stimulated eotaxin-3 mRNA expression levels in (A) EoE1-T and (B) EoE2-T cell lines as determined by conventional PCR and quantitative real-time PCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:53:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/538207"], "description"=>"<p>Data are the mean ± SEM of 2 separate experiments. ***, p≤0.001 compared to unstimulated (baseline) control, <sup>+++</sup>, p≤0.001 compared to IL-4 stimulation alone. Unstim.; unstimulated cells.</p>", "links"=>[], "tags"=>["decreases", "il-4-stimulated", "eotaxin-3", "secretion", "intelomerase-immortalized", "esophageal", "squamous", "lines", "patients", "eoe1-t"], "article_id"=>208678, "categories"=>["Molecular Biology", "Biochemistry", "Chemistry", "Cell Biology"], "users"=>["Xi Zhang", "Edaire Cheng", "Xiaofang Huo", "Chunhua Yu", "Qiuyang Zhang", "Thai H. Pham", "David H. Wang", "Stuart J. Spechler", "Rhonda F. Souza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050037.g002", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Omeprazole_decreases_IL_4_stimulated_eotaxin_3_protein_secretion_intelomerase_immortalized_esophageal_squamous_cell_lines_from_two_patients_with_EoE_A_EoE1_T_and_2_EoE2_T_/208678", "title"=>"Omeprazole decreases IL-4-stimulated eotaxin-3 protein secretion intelomerase-immortalized esophageal squamous cell lines from two patients with EoE, (A) EoE1-T and (2) EoE2-T.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:52:21"}
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  • {"files"=>["https://ndownloader.figshare.com/files/538537"], "description"=>"<p>mRNA expression levels were determined by quantitative real-time PCR in (A) EoE1-T and (B) EoE2-T cells. Data are the means ± SEM of 3 separate experiments assayed in triplicate. Representative experiments of Western blotting for (C) phospho- and total STAT6 in whole cell lysates and (D) phospho-STAT6 in nuclear lysates in EoE1-T and EoE2-T cells. Tubulin and lamin A/C served as controls for the whole cell and nuclear lysates, respectively. Unstim., unstimulated cells.</p>", "links"=>[], "tags"=>["il-4-stimulated", "eotaxin-3", "mrna", "stat6", "phosphorylation", "nulcear", "translocation", "eoe1-t", "eoe2-t"], "article_id"=>209009, "categories"=>["Molecular Biology", "Biochemistry", "Chemistry", "Cell Biology"], "users"=>["Xi Zhang", "Edaire Cheng", "Xiaofang Huo", "Chunhua Yu", "Qiuyang Zhang", "Thai H. Pham", "David H. Wang", "Stuart J. Spechler", "Rhonda F. Souza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050037.g005", "stats"=>{"downloads"=>1, "page_views"=>97, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Omeprazole_Ome_does_not_increase_IL_4_stimulated_eotaxin_3_mRNA_degradation_and_does_not_decrease_STAT6_phosphorylation_or_nulcear_translocation_in_EoE1_T_and_EoE2_T_cell_lines_/209009", "title"=>"Omeprazole (Ome) does not increase IL-4-stimulated eotaxin-3 mRNA degradation, and does not decrease STAT6 phosphorylation or nulcear translocation in EoE1-T and EoE2-T cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:54:04"}
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  • {"files"=>["https://ndownloader.figshare.com/files/538312"], "description"=>"<p>Data are the mean ± SEM of at least 2 separate experiments. ***, p≤0.001 compared to unstimulated (baseline) control, <sup>+++</sup>, p≤0.001 compared to IL-4 stimulation alone. Unstim., unstimulated cells.</p>", "links"=>[], "tags"=>["decreases", "il-4-stimulated", "eotaxin-3", "secretion", "eoe1-t", "eoe2-t"], "article_id"=>208792, "categories"=>["Molecular Biology", "Biochemistry", "Chemistry", "Cell Biology"], "users"=>["Xi Zhang", "Edaire Cheng", "Xiaofang Huo", "Chunhua Yu", "Qiuyang Zhang", "Thai H. Pham", "David H. Wang", "Stuart J. Spechler", "Rhonda F. Souza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050037.g003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lansoprazole_decreases_IL_4_stimulated_eotaxin_3_protein_secretion_in_A_EoE1_T_and_2_EoE2_T_cells_/208792", "title"=>"Lansoprazole decreases IL-4-stimulated eotaxin-3 protein secretion in (A) EoE1-T and (2) EoE2-T cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:52:55"}

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Relative Metric

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