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Transcription Regulation of Inflammation by Glucocorticoids

Institution: University of California, Berkeley
Investigator(s): Jen-Chywan Wang, Ph.D
Award Cycle: 2008 (Cycle 17) Grant #: 17KT-0028 Award: $270,000
Subject Area: Pulmonary Disease
Award Type: New Investigator Awards

Initial Award Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease in which lungs are damaged and make it hard to breathe. Inflammation plays an important part in the development of COPD. Currently there is no cure for COPD. However, we can slow down or relieve the symptom by decreasing inflammation.

MKP-1 is a protein that can suppress inflammation. The activity of MKP-1 mainly depends on its amount in cells. Changing the amount of MKP-1 protein, thus, strongly influences how our body handles inflammatory responses. The production of MKP-1 protein in cells is stringently controlled. The information that tells the body which proteins to make is stored in the form of DNA; the information for each protein is coded for by a specific piece of DNA called a gene. There are two biochemical processes involved in converting the DNA code into a protein molecule. These are called 'transcription' and 'translation'. The production of MKP-1 protein is regulated at the 'transcription' process.

This proposal will explore how MKP-1 gene transcription is regulated. Notably, MKP-1 gene transcription is induced by steroid hormones, glucocorticoids. Glucocorticoids are commonly used to treat a wide variety of inflammatory diseases, including COPD, because of their strong ability to inhibit inflammation. One reason that glucocorticoids can suppress inflammation is because they increase MKP-1 gene transcription. However, “how” glucocorticoids increase MKP-1 gene transcription is not known. In this proposal, we will also study this question.

Overall, this proposal is important from both basic science and clinical perspective. A potential therapy for treating inflammatory diseases, such as COPD, is to increase MKP-1 protein levels in cells. Therefore, understanding how MKP-1 gene transcription is regulated is an important topic.

Transcriptional regulation of human dual specificity protein phosphatase 1 (DUSP1) gene by glucocorticoids, in revision
Periodical: PLOS One Index Medicus:
Authors: Shipp LE, Yu CY, Lee JV, Pufall M, Zhang P, Scott DK, Wang JC ART
Yr: 2010 Vol: Nbr: Abs: Pg: