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Enhanced production of prostaglandin E2 (PGE2) by alveolar macrophage (AM) harvested from silica-exposed rats: possible regulatory role of nitric oxide (NO).
Ma-JYC; Yang-HM; Barger-MW; Ma-JKH; Castranova-V
FASEB J 1999 Mar; 13(4)(Part 1):A505
This study investigated whether NO plays a significant role in regulating the production of PGE2, or inflammatory cytokines by silica-exposed AM. Rats were treated by intratracheal instillation of saline (control) or silica (20 mg/rat) and AM harvested by bronchoalveolar lavage at I, 3, 7, 14, and 28 days post-exposure. AM were cultured for 24 br and ex vivo production of PGE2 leukotriene B4 (LTB4), TNF-A, IL-1 , and NO were monitored. In vivo exposure to silica resulted in an increase in PGE, production which peaked (185 fold) at 3 days postexposure, while LTB4 release was decreased. Silica exposure incn:ased NO production by 9 fold at 3 days postexposure, while causing a moderate increase in TNF -4 production and a significant elevation of IL-1 secretion which was sustained through 28 days post-exposure. Tetrandrine, an antifibrotic agent, inhibited IL-1 and TNF-4 production but did not affect NO or PGE2 release. Indomethacin blocked PGE, production completely and bad a moderate effect on NO production. Furthermore, inhibition of NO production with N-nitro-Larginine methyl ester enhanced PGE, production without affecting TNF -4 or IL-1 release. These results suggest that silica-induced stimulation of PGE, production is controlled via a different pathway than cytokine production and that NO may play a role in limiting PGE2 production in silica-exposed rats.
Laboratory-animals; Animals; Animal-studies; Inhalation-studies; Exposure-levels; Exposure-assessment; Dose-response; Silicates; Silica-dusts; Silicosis; Alveolar-cells
Abstract; Conference/Symposia Proceedings
Issue of Publication
The FASEB Journal