Regulated production of the T helper 2-type T-cell chemoattractant TARC by human bronchial epithelial cells in vitro and in human lung xenografts

M. C. Berin, L. Eckmann, D. H. Broide, M. F. Kagnoff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

The chemokine TARC is a ligand for the chemokine receptor CCR4 expressed on T helper (Th)2-type CD4 T cells. Allergic airway inflammation is characterized by a local increase in cells secreting Th2-type cytokines. We hypothesized that bronchial epithelial cells may be a source of chemokines known to chemoattract Th2 cells. Regulated TARC expression was studied using normal human bronchial epithelial cells and a human lung xenograft model. TARC expression was increased in normal human bronchial epithelial cells in response to tumor necrosis factor-α stimulation, and further upregulation of TARC was observed with interferon (IFN)-γ but not interleukin (IL)-4 costimulation. TARC functions as a nuclear factor (NF)-κB target gene, as shown by the abrogation of TARC expression in response to proinflammatory stimuli when NF-κB activation is inhibited. In an in vivo model, minimal constitutive TARC expression was observed in human lung xenografts. Consistent with our findings in vitro, TARC messenger RNA (mRNA) expression was upregulated in the xenografts in response to IL-1, and costimulation with IFN-γ but not IL-4 further increased TARC mRNA and protein expression. In addition, bronchoalveolar lavage fluid from asthmatic subjects after allergen challenge contained significantly increased levels of TARC, suggesting that TARC production by bronchial epithelial cells may play a role in the pathogenesis of allergic asthma.

Original languageEnglish (US)
Pages (from-to)382-389
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume24
Issue number4
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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