Silica-induced pulmonary inflammation in rats: activation of NF-kappa B and its suppression by dexamethasone

Biochem Biophys Res Commun. 1998 Dec 9;253(1):181-4. doi: 10.1006/bbrc.1998.9763.


The goal of this study was to examine the relationship of the transcriptional regulatory factor nuclear factor-kappaB (NF-kappa B) to the early inflammatory events involved with silica exposure. Male F-344 rats received an intratracheal (i.t.) instillation of silica (100 mg/kg in a volume of 1 ml/kg) of saline. At 1, 3, 6, and 18 h postinstillation, and the rats were sacrificed and underwent bronchoalveolar lavage (BAL) for functional analysis of inflammation. Beginning at 1 h postinstillation, the silica-instilled (Si) rats displayed significant increases in neutrophils in BAL fluid compared to the saline controls. BAL cells from the Si group displayed a significant increase in luminol-dependent chemiluminescence (LDCL) compared to the controls. NF-kappa B activation was measurable at 3 h postinstillation, and this activation continued throughout the 18-h time course. Treatment with dexamethasone (5 mg/kg) at -3 h prior to silica instillation, at the time of instillation (0 h), and +1.5 h postinstillation resulted in both a reduction in NF-kappa B expression (by 70%) at 3 h postinstillation and corresponding reductions in LDCL, BAL cell count, and BAL neutrophils. These results show that activation of NF-kappa B is associated with silica-induced pulmonary inflammation, and the inhibition of its activation correlates temporally with suppression of inflammation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count / drug effects
  • Cell Differentiation / drug effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacology*
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Injections, Intraperitoneal
  • Intubation, Intratracheal
  • Luminescent Measurements
  • Luminol / metabolism
  • Lung / drug effects
  • Lung / metabolism*
  • Lung / pathology*
  • Male
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / biosynthesis
  • NF-kappa B / metabolism*
  • Rats
  • Rats, Inbred F344
  • Silicon Dioxide / toxicity*


  • Anti-Inflammatory Agents
  • NF-kappa B
  • Luminol
  • Silicon Dioxide
  • Dexamethasone