IL-1beta induces eotaxin gene transcription in A549 airway epithelial cells through NF-kappaB.
Publication/Presentation Date
12-1-2000
Abstract
Eotaxin is an asthma-related C-C chemokine that is produced in response to interleukin-1beta (IL-1beta). We detected an increase in newly transcribed eotaxin mRNA in IL-1beta-stimulated airway epithelial cells. Transient transfection assays using promoter-reporter constructs identified a region as essential for IL-1beta-induced increases in eotaxin transcription. Using site-directed mutagenesis, we found that a nuclear factor-kappaB (NF-kappaB) site located 46 bp upstream from the transcriptional start site was both necessary and sufficient for IL-1beta induction of reporter construct activity. Electrophoretic mobility shift assay demonstrated that IL-1beta-stimulated airway epithelial cells produced p50 and p65 protein that bound this site in a sequence-specific manner. The functional importance of the NF-kappaB site was demonstrated by coexpression experiments in which increasing doses of p65 expression vector were directly associated with reporter activity exclusively in constructs with an intact NF-kappaB site (r(2) = 0.97, P = 0.002). Moreover, IL-1beta-induced increases in eotaxin mRNA expression are inhibited by inhibitors of NF-kappaB. Our findings implicate NF-kappaB and its binding sequence in IL-1beta-induced transcriptional activation of the eotaxin gene.
Volume
279
Issue
6
First Page
1058
Last Page
1065
ISSN
1040-0605
Published In/Presented At
Jedrzkiewicz, S., Nakamura, H., Silverman, E. S., Luster, A. D., Mansharamani, N., In, K. H., Tamura, G., & Lilly, C. M. (2000). IL-1beta induces eotaxin gene transcription in A549 airway epithelial cells through NF-kappaB. American journal of physiology. Lung cellular and molecular physiology, 279(6), L1058–L1065. https://doi.org/10.1152/ajplung.2000.279.6.L1058
Disciplines
Medicine and Health Sciences
PubMedID
11076795
Department(s)
Department of Medicine
Document Type
Article