Silica-induced pulmonary inflammation in rats: activation of NF-kappa B and its suppression by dexamethasone.
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.
Sacks
M
M
Program in Genetics and Developmental Biology, West Virginia University, Morgantown 26506, USA. mreasor@hsc.wvu.edu
Gordon
J
J
Bylander
J
J
Porter
D
D
Shi
X L
XL
Castranova
V
V
Kaczmarczyk
W
W
Van Dyke
K
K
Reasor
M J
MJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D007442:Intubation, Intratracheal; D008163:Luminescent Measurements; D008165:Luminol / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012822:Silicon Dioxide / Q000633:toxicity*
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D008165:Luminol; D012822:Silicon Dioxide; D003907:Dexamethasone