Hypertonic saline attenuates TNF-alpha-induced NF-kappaB activation in pulmonary epithelial cells

Shock. 2009 May;31(5):466-72. doi: 10.1097/SHK.0b013e31818ec47d.


Resuscitation with hypertonic saline (HTS) attenuates acute lung injury (ALI) and modulates postinjury hyperinflammation. TNF-alpha-stimulated pulmonary epithelium is a major contributor to hemorrhage-induced ALI. We hypothesized that HTS would inhibit TNF-alpha-induced nuclear factor (NF)-kappaB proinflammatory signaling in pulmonary epithelial cells. Therefore, we pretreated human pulmonary epithelial cells (A549) with hypertonic medium (180 mM NaCl) for 30 min, followed by TNF-alpha stimulation (10 ng/mL). Key regulatory steps and protein concentrations in this pathway were assessed for significant alterations. Hypertonic saline significantly reduced TNF-alpha-induced intercellular adhesion molecule 1 levels and NF-kappaB nuclear localization. The mechanism is attenuated phosphorylation and delayed degradation of IkappaB alpha. Hypertonic saline did not alter TNF-alpha-induced p38 mitogen-activated protein kinase phosphorylation or constitutive vascular endothelial growth factor expression, suggesting that the observed inhibition is not a generalized suppression of protein phosphorylation or cellular function. These results show that HTS inhibits TNF-alpha-induced NF-kappaB activation in the pulmonary epithelium and, further, our understanding of its beneficial effects in hemorrhage-induced ALI.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Blotting, Western
  • Cell Line
  • Cell Survival / drug effects
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism*
  • Flow Cytometry
  • Humans
  • Lung / cytology*
  • Microscopy, Fluorescence
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • Saline Solution, Hypertonic / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology*


  • NF-kappa B
  • Saline Solution, Hypertonic
  • Tumor Necrosis Factor-alpha