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Mechanisms of molecular regulation o...

Keen, Judith Clancy.

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Mechanisms of molecular regulation of interleukin-4 and interleukin-13 gene expression: The role of NFAT and its implication in the development of allergic asthma.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Mechanisms of molecular regulation of interleukin-4 and interleukin-13 gene expression: The role of NFAT and its implication in the development of allergic asthma./
Author:	Keen, Judith Clancy.
Description:	204 p.
Notes:	Advisers: Steve N. Georas; Marsha Wills-Karp.
Contained By:	Dissertation Abstracts International62-10B.
Subject:	Health Sciences, Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3028291
ISBN:	0493403426

Mechanisms of molecular regulation of interleukin-4 and interleukin-13 gene expression: The role of NFAT and its implication in the development of allergic asthma.
Keen, Judith Clancy.

Mechanisms of molecular regulation of interleukin-4 and interleukin-13 gene expression: The role of NFAT and its implication in the development of allergic asthma. - 204 p.

Advisers: Steve N. Georas; Marsha Wills-Karp.

Thesis (Ph.D.)--The Johns Hopkins University, 2002.

It has long been known that human asthmatics, even those with mild asthma, have increased influx of CD4+ Th2 cells into the lung. Genetic linkage analysis, in numerous cohorts worldwide has revealed a prominent linkage to a region on human Chromosome 5q that encodes the Th2 cytokine genes including Interleukin (IL)-4 and IL-13. Indeed, expression of these Th2 cytokines is elevated in both the bronchial biopsy and in the bronchoalveolar lavage fluid of asthmatics, suggesting that the regulation of gene expression of these cytokines is altered leading to aberrant gene expression in asthmatics. Here we provide evidence that Th2 cytokine gene expression is regulated at the transcriptional level through the interaction of transcription factors with the promoter regions. We hypothesize that transcriptional dysregulation of IL-4 and IL-13 gene expression leads to their aberrant expression and the development of airway hyperreactivity. To date little is known about in vivo regulation of these genes and the influence of the local cytokine microenvironment on gene expression. We provide evidence that IL-4 gene expression in a mouse model of asthma is dependent on the cytokine milieu of the splenic microenvironment, which works by altering transcription factor activation and interaction with the promoter region. This suggests that cytokines in the splenic microenvironment including IL-10 and IL-12 play an important role in regulating transcription factor activation and IL-4 gene expression. We propose that understanding the molecular regulation of these genes and the potential pathways involved in their activation in a mouse model will lead to understanding alterations in human asthma and could potentially lead to rational drug therapy to prevent development of airway hyperreactivity.

ISBN: 0493403426Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Mechanisms of molecular regulation of interleukin-4 and interleukin-13 gene expression: The role of NFAT and its implication in the development of allergic asthma.
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035 $a (UnM)AAI3028291
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100 1 $a Keen, Judith Clancy. $3 1251209
245 1 0 $a Mechanisms of molecular regulation of interleukin-4 and interleukin-13 gene expression: The role of NFAT and its implication in the development of allergic asthma.
300 $a 204 p.
500 $a Advisers: Steve N. Georas; Marsha Wills-Karp.
500 $a Source: Dissertation Abstracts International, Volume: 62-10, Section: B, page: 4453.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2002.
520 $a It has long been known that human asthmatics, even those with mild asthma, have increased influx of CD4+ Th2 cells into the lung. Genetic linkage analysis, in numerous cohorts worldwide has revealed a prominent linkage to a region on human Chromosome 5q that encodes the Th2 cytokine genes including Interleukin (IL)-4 and IL-13. Indeed, expression of these Th2 cytokines is elevated in both the bronchial biopsy and in the bronchoalveolar lavage fluid of asthmatics, suggesting that the regulation of gene expression of these cytokines is altered leading to aberrant gene expression in asthmatics. Here we provide evidence that Th2 cytokine gene expression is regulated at the transcriptional level through the interaction of transcription factors with the promoter regions. We hypothesize that transcriptional dysregulation of IL-4 and IL-13 gene expression leads to their aberrant expression and the development of airway hyperreactivity. To date little is known about in vivo regulation of these genes and the influence of the local cytokine microenvironment on gene expression. We provide evidence that IL-4 gene expression in a mouse model of asthma is dependent on the cytokine milieu of the splenic microenvironment, which works by altering transcription factor activation and interaction with the promoter region. This suggests that cytokines in the splenic microenvironment including IL-10 and IL-12 play an important role in regulating transcription factor activation and IL-4 gene expression. We propose that understanding the molecular regulation of these genes and the potential pathways involved in their activation in a mouse model will lead to understanding alterations in human asthma and could potentially lead to rational drug therapy to prevent development of airway hyperreactivity.
590 $a School code: 0098.
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0982
710 2 0 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 62-10B.
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790 1 0 $a Georas, Steve N., $e advisor
790 1 0 $a Wills-Karp, Marsha, $e advisor
791 $a Ph.D.
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856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3028291