Differential regulation of eotaxin expression by IFN-γ in airway epithelial cells

Satoshi Matsukura, Fumio Kokubu, Hideki Kuga, Mio Kawaguchi, Koushi Ieki, Miho Odaka, Shintarou Suzuki, Shin Watanabe, Hiroko Takeuchi, Mitsuru Adachi, Cristiana Stellato, Robert P. Schleimer

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Eotaxin is a chemokine that binds with high affinity and specificity to the chemokine receptor CCR3 and plays an important role in the pathogenesis of allergic disease. Objective: We studied the regulation of eotaxin expression by the TH1 cytokine IFN-γ and analyzed its molecular mechanisms. Methods: Levels of eotaxin mRNA and protein expression in the airway epithelial cell line BEAS-2B were determined with RT-PCR and ELISA. Mechanisms of transcriptional regulation were assessed by means of electrophoretic mobility shift assays and luciferase assay with eotaxin promoter-luciferase reporter plasmids. Results: Although IFN-γ did not directly induce the expression of eotaxin protein, it increased the induction by TNF-α when these cytokines were added simultaneously. In contrast, preincubation of cells with IFN-γ for 24 hours profoundly inhibited the production induced by TNF-α. IFN-γ did not influence the TNF-α-induced binding of nuclear factor κB to a DNA probe derived from the eotaxin promoter. IFN-γ did not increase the ability of TNF-α to activate the eotaxin promoter. Studies of eotaxin mRNA levels indicate that IFN-γ combined with TNF-α increased the expression of eotaxin mRNA. When cells were preincubated with IFN-γ, there was no inhibition of the appearance of eotaxin mRNA. Conclusion: These studies demonstrate that IFN-γ enhances eotaxin expression when added in combination with TNF-α and profoundly inhibits eotaxin expression after preincubation. In both cases the available data indicate that the effect is mediated by a posttranscriptional mechanism.

Original languageEnglish (US)
Pages (from-to)1337-1344
Number of pages8
JournalThe Journal of Allergy and Clinical Immunology
Volume111
Issue number6
DOIs
StatePublished - Jun 1 2003

Keywords

  • Asthma
  • Eotaxin
  • Epithelial cells
  • IFN-γ

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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