IL-1β induces eotaxin gene transcription in A549 airway epithelial cells through NF-κB

Sean Jedrzkiewicz, Hidetoshi Nakamura, Eric S. Silverman, Andrew D. Luster, Naresh Mansharamani, Kwang Ho In, Gen Tamura, Craig M. Lilly

    Research output: Contribution to journalArticlepeer-review

    43 Citations (Scopus)

    Abstract

    Eotaxin is an asthma-related C-C chemokine that is produced in response to interleukin-1β (IL-1β). We detected an increase in newly transcribed eotaxin mRNA in IL-1β-stimulated airway epithelial cells. Transient transfection assays using promoter-reporter constructs identified a region as essential for IL-1β-induced increases in eotaxin transcription. Using site-directed mutagenesis, we found that a nuclear factor-κB (NF-κB) site located 46 bp upstream from the transcriptional start site was both necessary and sufficient for IL-1β induction of reporter construct activity. Electrophoretic mobility shift assay demonstrated that IL-1β-stimulated airway epithelial cells produced p50 and p65 protein that bound this site in a sequence-specific manner. The functional importance of the NF-κB 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-κB site (r2 = 0.97, P = 0.002). Moreover, IL-1β-induced increases in eotaxin mRNA expression are inhibited by inhibitors of NF-κB. Our findings implicate NF-κB and its binding sequence in IL-1β-induced transcriptional activation of the eotaxin gene.

    Original languageEnglish
    Pages (from-to)L1058-L1065
    JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
    Volume279
    Issue number6 23-6
    DOIs
    Publication statusPublished - 2000

    Keywords

    • Asthma
    • Chemokine
    • Cytokine
    • Eosinophil

    ASJC Scopus subject areas

    • Physiology
    • Pulmonary and Respiratory Medicine
    • Physiology (medical)
    • Cell Biology

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