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Nuclear factor-kappa beta (NF-KB) activity in rat alveolar macrophages exposed to respirable organic particles and antioxidants.
Ufferfilge-D; Cosma-GN; Gardner-H; Vallyathan-V
Toxicologist 1999 Mar; 48(1-S):310
Activation of the transcription factor NF-kB by respirable organic particles (ROP) facilitates oxidative damage in lung through increased expression of pro-inflammatory genes. In previous studies, we found that NF-kB in alveolar macrophages was activated maximally at 2 hours following in vitro treatments with ROP. Because of the recent interest in identifying oxygen radical pathways of NF-kB activation, we have investigated inhibitory effects by specific antioxidant agents. NR8383 rat alveolar macrophage cells were treated with ROP, with and without antioxidants, and analyzed for NF-kB activation employing the electrophoretic mobility shift assay (EMSA). Densitometry analysis of EMSA gels revealed the following reductions in NF-KB activation (reported as % of positive control). 200 units/ml superoxide dismutase reduced activation by 51 %, whereas catalase had no inhibitory effect, strongly suggesting a primary role for the superoxide anion radical but not hydrogen peroxide, in the activation of NF-kB in alveolar macrophages. Furthermore, only a 270/0 reduction in NF-kB activation was observed following cell treatments with 1 nM melatonin, an efficient scavenger of hydrogen peroxide. A series of vitamin E species, alphatocopherol succinate, vitamin E acetate, and Trolox a vitamin E derivative, at 100 microM reduced NF-kB activation 63%, 33%, and 38%, respectively, clearly indicating that vitamin E analogs differ in their potencies of NF-kB inhibition. One microM pyrroHdinedithiocarbamate and 20 mM N-acetyl cysteine, which have effects on diverse oxygen free radical pathways, reduced NF-kB activation 54% and 66%, respectively, providing further support for a general role of reactive oxygen species in NF-kB activation. Ongoing studies are exploring the rote of lipopolysaccharide receptors and calcium regulatory pathways on NF-kB activation in lung cells following exposure to particulate matter.
Animal-studies; Laboratory-animals; Statistical-analysis; Analytical-methods; Analytical-chemistry; Exposure-assessment; Toxicology; Toxins; Toxic-materials; Antioxidants; Antioxidation; Cell-transformation; Cellular-reactions; Particulate-dust; Airborne-particles
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana
LA; WV; MD; CO
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