Version 2.1.1.0

Abstract

Grant Number:	5R42HL064536-03
PI Name:	BRIGHAM, KENNETH L.
PI Email:	kbrigha@emory.edu
PI Title:	PROFESSOR OF MEDICINE
Project Title:	p20, Molecular Shortstop for Inflammatory Lung Diseases

Abstract: DESCRIPTION (Applicant's abstract): The transcription factor CAAT enhancer binding protein beta (C/EBPbeta) is a key factor orchestrating the inflammatory response. Specifically, expression of the genes encoding the pro-inflammatory cytokines IL-6 and on IL-8 are regulated by C/EBPbeta. C/EBPbeta can be either an activator or an inhibitor of inflammation depending on the dominant isoforms produced. Our data indicate that airway epithelial cells in culture terminate production of IL-6 and IL-8 increasing production of inhibitory C/EBPbeta isoform (p20) and that cells that have an exaggerated inflammatory response produce decreased amounts of this isoform. In addition, when animals are given endotoxin there is a decrease in lung production of the inhibitory C/EBPbeta isoform and an increase in production of the activator isoform. Since IL-6 production correlates with severity of sepsis in humans and interventions that decrease IL-6 improve outcome in that setting, we believe that increasing the inhibitory C/EBPbeta isoform in the lungs could be therapeutic for the pulmonary complications of sepsis.

Thesaurus Terms:
antiinflammatory agent, drug design /synthesis /production, gene delivery system, gene therapy, inflammation, lung disorder, transcription factor
adult respiratory distress syndrome, cystic fibrosis, interleukin 6, interleukin 8, liposome, recombinant protein, respiratory epithelium, transfection, transfection /expression vector

Institution:	GENERX+, INC.
	3200 WEST END AVE, STE 500
	NASHVILLE, TN 372011322
Fiscal Year:	2003
Department:
Project Start:	20-MAY-2000
Project End:	31-JUL-2004
ICD:	NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
IRG:	ZRG1

---