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

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Thulasiraman, Padmamalini

Contributors dc:contributor

• Shapiro, David J.

• Chemistry, Biochemistry

Language dc:language

eng

Identifier

(MiAaPQ)AAI3086200

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84794