Meir S. Sacks

Date of Graduation


Document Type



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