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Effects of the lung carcinogen silica on cyclooxygenase-2 and prostaglandin E2 expression in RAW 264.7 cells.
Harris-GK; Zhang-Z; Shi-X
Proceedings of the 93rd American Association for Cancer Research Annual Meeting, April 6-10, 2002, San Francisco, California. Philadelphia, PA: American Association for Cancer Research, 2002 Apr; 43:470
Silica is a mineral which is associated with a number of lung diseases, including lung cancer, mesothelioma and silicosis. Elevated levels of the proteins Cyclooxygenase-2 (Cox-2) and Prostaglandin E2 (PGE2) synthase have been observed in lung cancer in a number of in vitro and in vivo studies. Few studies have examined the link between silica exposure and the expression of Cox-2 and PGE2 synthase, however. The purpose of this study was to investigate the effects of silica on Cox-2 and PGE2 synthase expression in RAW 264.7 mouse macrophage cells. RAW cells were incubated with silica at 0, 10, 50, 100 or 1,000 microg/ml for 12 hours. As a positive control for Cox-2 expression, lipopolysaccharide (LPS) was administered for 12 hours to a 6th treatment group at 10 microg/ml. Silica treatment induced Cox-2 and PGE2 protein expression in a dose-dependent manner. The highest dose silica-treated group induced Cox-2 to a greater degree, than did the LPS positive control. Based on previous studies in our laboratory which indicated that silica affects signal transduction pathways upstream of Cox-2, particularly those associated with MAP Kinase pathways, further studies were conducted using specific inhibitors. Using the highest (1,000 microg/ml silica dose, the inhibitors SB 203580 (a p38 MAP Kinase Inhibitor), PD 98059 (a MEK1 Inhibitor for ERK), UO126 (an ERK inhibitor), Calpain Inhibitor I (an NFkB Inhibitor), and Cannabinol (a CREB/ATF:1 Inhibitor) were tested for their effects on Cox-2 expression. Only SB 203580 attenuated Cox-2 protein expression. The results of this study indicate that silica exposure induces both Cox-2 and PGE2 expression and that silica-induced Cox-2 expression is partially dependent on p38 MAP Kinase.
Cancer; In-vitro-study; Cell-cultures; Cell-damage; Cell-alteration; Cellular-reactions; Lung-cancer; Mesothelial-cells; Silicosis; Silica-dusts; Protein-synthesis; Proteins; Prostaglandin-inhibitors; Dose-response; Carcinogens
Abstract; Conference/Symposia Proceedings
Research Tools and Approaches: Cancer Research Methods
Proceedings of the 93rd American Association for Cancer Research Annual Meeting, April 6-10, 2002, San Francisco, California
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division