Modulators of Inflammation and Steroid Receptors Regulate Proteinase Inhibitor 9 Gene Expression

Thulasiraman, Padmamalini

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Description

Title

Modulators of Inflammation and Steroid Receptors Regulate Proteinase Inhibitor 9 Gene Expression

Author(s)

Thulasiraman, Padmamalini

Issue Date

2003

Doctoral Committee Chair(s)

Shapiro, David J.

Department of Study

Biochemistry

Discipline

Biochemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Chemistry, Biochemistry

Language

eng

Abstract

In addition to pro-inflammatory agents, the synthetic anti-inflammatory glucocorticoid, dexamethasone, induced PI-9 gene expression via an imperfect glucocorticoid response element (GRE) located at -208. Dexamethasone induced PI-9 mRNA and protein. Dexamethasone-glucocorticoid receptor (GR) complex inhibited IL-1beta induced PI-9 gene expression but IL-1beta did not interfere with dexamethasone induction of PI-9. Glucocorticoid administration resulted in reduced p65 binding to a consensus NF-kappaB element. To investigate the mechanism of crosstalk between Dex-GR and NF-kappaB, we analyzed the effect of dexamethasone on induction of IkappaB-alpha, the inhibitory heterodimer of p65. Dexamethasone induced IkappaBalpha in HepG2 cells. This may be one of the mechanisms used by Dex-GR to interfere with NF-kappaB activity and block IL-1beta-induced PI-9 gene expression. Our findings show that liganded GR may regulate IL-1beta induction of PI-9 expression through NF-kappaB and AP-1 transcription factors by a mechanism quite different than that seen for estrogen-ER.

Graduation Semester

2003

Type of Resource

text

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