Calcium-dependent regulation of NF-κB activation in cystic fibrosis airway epithelial cells

Olivier Tabary, Emilie Boncoeur, Rainer De Martin, Rainer Pepperkok, Annick Clément, Carsten Schultz, Jacky Jacquot

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Dysregulation of nuclear factor kappa B (NF-κB) and increased Ca2+ signals have been reported in airway epithelial cells of patients with cystic fibrosis (CF). The hypothesis that Ca2+ signaling may regulate NF-κB activation was tested in a CF bronchial epithelial cell line (IB3-1, CFTR genotype ΔF508/W1282X) and compared to the CFTR-corrected epithelial cell line S9 using fluorescence microscopy to visualized in situ NF-κB activation at the single cell level. Upon stimulation with IL-1β, we observed a slow but prolonged [Ca2+]i increase (up to 10 min) in IB3-1 cells compared to S9 cells. The IL-1β-induced [Ca2+]i response was accompanied by an activation of NF-κB in IB3-1 but not in S9 cells. Pretreatment of IB3-1 cells with the ER Ca2+ pump inhibitor thapsigargin inhibited the IL-1β-induced [Ca2+]i response. Treatment with either the calcium chelator BAPTA or an inhibitor of IκBα phosphorylation (digitoxin) led to a drastic [Ca2+]i decrease accompanied by an inhibition of NF- κB activation of IL-1β-stimulated IB3-1 cells in comparison to untreated cells. In IB3-1 cells cultured at low temperature (26°C) for 16 h, the IL-1β-induced [Ca2+]i response was inhibited and no significant NF-κB activation was observed. To our knowledge, this is the first report of visualization of the Ca2+-mediated activation of NF-κB in individual living airway epithelial cells. Our results support the concept that [Ca 2+]i is a key regulator of NF-κB activation in CF airway epithelial cells.

Original languageEnglish (US)
Pages (from-to)652-660
Number of pages9
JournalCellular Signalling
Volume18
Issue number5
DOIs
StatePublished - May 1 2006

Keywords

  • CF airway epithelial cells
  • Calcium
  • Fluorescence microscopy
  • NF-B activation

ASJC Scopus subject areas

  • Cell Biology

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