Silica-induced pulmonary inflammation in rats: activation of NF Kappa B and its supression by dexamethasone.
Sacks M; Gordon J; Bylander J; Porter D; Shi XL; Castranova V; Kazmarczyk W; Reasor MJ; Van Dyke K
Toxicologist 1998 Mar; 42(1-S):350
Inhalation of silica is characterized by initial pulmonary inflammation leading to fibrosis. The goal of this study was to determine the relationship of the transcriptional regulatory factor, nuclear factor kappa B (NFkB) to the early inflammatory events involved with silica exposure. Male F-344 rats received an intratracheal of silica (2Omg/0.5ml) or saline. At 1, 3, 6 and 18 hours post-installation, the rats underwent broncheoalveolar lavage (BAL) for analysis of inflammation. From 3 hours post-instillation and onward, the silica-instilled (51) rats showed significant increases in BAL fluid neutrophil and lymphocyte counts as compared to the saline controls. BAL fluid cells from the 51 group also showed a significant increase in luminol-dependent chemiluminescence (LDCL) as compared to the controls. NFkB was present at 3 hours post- instillation and continued throughout the 18 hour time course. Dexamethasone (Dex) has been shown to inhibit NFkB expression invitro, but this has not been examined in the lung in-vivo. Treatment with Dex (5mg/kg) at - 3 and 0 hours prior to silica instillation and + 1.5 hour post instillation resulted in both a reduction in NFkB expression (by 70%) at 3 hours post-instillation as well as corresponding reductions in LDCL. BAL fluid cell count and BAL fluid inflammatory cells. These results show silica-induced pulmonary inflammation is associated with activation of NFkB and the inhibition of its activation correlates with suppression of inflammation.
Silicates; Silica-dusts; Silicosis; Fibrosis; Pulmonary-system; Pulmonary-function; Pulmonary-disorders; Pulmonary-congestion; Animal-studies; Animals; Laboratory-animals; Laboratory-testing
The Toxicologist. Society of Toxicology 37th Annual Meeting, March 1-5,1998, Seattle, Washington