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Michael Wourms Final Thesis.pdf (727.88 KB)

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The Aryl Hydrocarbon Receptor Regulates an Essential Transcriptional Element in the Immunoglobulin Heavy Chain Gene

Wourms, Michael J.
http://rave.ohiolink.edu/etdc/view?acc_num=wright1389551618

Abstract Details

2013, Master of Science (MS), Wright State University, Pharmacology and Toxicology.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that inhibits immunoglobulin (Ig) expression and Ig heavy (IgH) chain gene transcription. Transcription of the IgH gene involves several regulatory elements including the 3'lgh regulatory region (3'lghRR) which is composed of four enhancers (hs3A, hs1,2, hs4, and hs3B). Dioxin responsive elements (DRE) in the hs4 and hs1,2 enhancers of the 3lghRR that bind the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates dioxin sensitive genes suggest that the 3'lghRR may be a transcriptional target of TCDD. The current study utilized an IgA secreting mouse B-cell line that stably expresses a γ 2b transgene regulated by the 3'lghRR (CH12.γ 2b-3'lghRR cells). Both shRNA knock down of AhR and an AhR antagonist (CH-223191) reduced TCDD-induced inhibition of endogenous IgA and the γ 2b transgene expression. With the growing number of immune-related disorders correlated with polymorphisms of the human hs1,2 enhancer, ubiquitously found AhR ligands, and sensitivity of human Ig expression to TCDD, our findings may provide indispensible information for human health risk assessment and insight into the development of therapeutic interventions for immune-related disease.
Courtney Sulentic, Ph.D. (Committee Chair)
Michael Leffak, Ph.D. (Committee Member)
Katherine Excoffon, Ph.D. (Committee Member)
45 p.
Immunology; Pharmacology; Toxicology
aryl hydrocarbon receptor; AhR; immune deficient; autoimmunity; TCDD; dioxin; ARNT; immunoglobulin regulatory region; immunoglobulin heavy chain; Cyp1A1

Recommended Citations

Citations

  • Wourms, M. J. (2013). The Aryl Hydrocarbon Receptor Regulates an Essential Transcriptional Element in the Immunoglobulin Heavy Chain Gene [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1389551618

    APA Style (7th edition)

  • Wourms, Michael. The Aryl Hydrocarbon Receptor Regulates an Essential Transcriptional Element in the Immunoglobulin Heavy Chain Gene. 2013. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1389551618.

    MLA Style (8th edition)

  • Wourms, Michael. "The Aryl Hydrocarbon Receptor Regulates an Essential Transcriptional Element in the Immunoglobulin Heavy Chain Gene." Master's thesis, Wright State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=wright1389551618

    Chicago Manual of Style (17th edition)

wright1389551618
583
© 2013, some rights reserved.Creative Commons License The Aryl Hydrocarbon Receptor Regulates an Essential Transcriptional Element in the Immunoglobulin Heavy Chain Gene by Michael J. Wourms is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Wright State University and OhioLINK.