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 journalArticle

40 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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    Jedrzkiewicz, S., Nakamura, H., Silverman, E. S., Luster, A. D., Mansharamani, N., In, K. H., Tamura, G., & Lilly, C. M. (2000). IL-1β induces eotaxin gene transcription in A549 airway epithelial cells through NF-κB. American Journal of Physiology - Lung Cellular and Molecular Physiology, 279(6 23-6), L1058-L1065. https://doi.org/10.1152/ajplung.2000.279.6.l1058