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Aryl hydrocarbon receptor signaling ...

McMillan, Brian J.

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Aryl hydrocarbon receptor signaling in immune and vascular biology.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Aryl hydrocarbon receptor signaling in immune and vascular biology./
作者:	McMillan, Brian J.
面頁冊數:	129 p.
附註:	Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2089.
Contained By:	Dissertation Abstracts International68-04B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3261375

Aryl hydrocarbon receptor signaling in immune and vascular biology.
McMillan, Brian J.

Aryl hydrocarbon receptor signaling in immune and vascular biology. - 129 p.

Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2089.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2007.

The aryl hydrocarbon receptor (AHR) is an evolutionarily conserved basic-helix-loop-helix (bHLH) transcription factor and member of the Per-ARNT-Sim (PAS) superfamily of environmental sensors. The AHR mediates (i) the vertebrate response to xenobiotic aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD, dioxin) and (ii) several diverse and poorly understood endogenous functions. Previous work has demonstrated that alteration of AHR signaling perturbs murine development of both T lymphocytes and vascular structure. Due to their common hemangioblast-lineage, vascular and immune cell types share several key features which may include similar AHR-regulated pathways. This thesis work has employed a series of approaches to elucidate AHR-mediated signaling in vascular and immune systems in response to both endogenous and exogenous stimuli. In the first chapter of this thesis, we review what is currently known regarding endogenous AHR function from work in the genetic model systems Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus. A critical review of this literature may clarify AHR function in eukaryote physiology, including insight into the pathways altered by toxic, xenobiotic agonists of the AHR. In chapter two, we explore the role of AHR signaling in mammalian T lymphocyte development. We characterize the effects of exogenous, superactivation of the AHR on hematopoietic differentiation within the thymus, most notably dysregulation of Kruppel-like factor-2 (KLF2), a central transcriptional regulator of hemangioblast-lineage biology. The documented roles of (i) the AHR in vascular development and (ii) KLF2 in the endothelial response to fluid shear stress led us to investigate AHR function in flow-mediated signaling. In chapter three, we establish that the AHR acts as a physiological sensor for a novel shear-induced modification of serum low-density lipoprotein (LDL). Moreover, we show that multiple routes of LDL modification are sufficient for AHR activation and provide evidence that Ahr genotype is linked to the presence of AHR-activating LDL in vivo. In chapter four, we present future approaches to further elucidate the major themes of this thesis.Subjects--Topical Terms:

1017719
Biology, Molecular.

Aryl hydrocarbon receptor signaling in immune and vascular biology.
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