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Involvement of NF-kappaB in silica-induced cyclooxygenase II gene expression in rat alveolar macrophages.
Chen F; Sun S; Kuhn DC; Gaydos LJ; Shi X; Lu Y; Demers LM
Am J Physiol, Lung Cell Mol Physiol 1997 Apr; 272(4):L779-L786
The role of nuclear factor (NF)-kappaB transcription factor in silica-induced cyclooxygenase (COX) II gene expression was examined in the rat alveolar macrophage cell line NR8383. Our results indicate that NF-kappaB can be activated in this cell line by silica exposure. Suppression of NF-kappaB activation in these cells leads to an attenuation of COX II mRNA accumulation induced by silica. Using an electrophoretic mobility shift assay and a reporter gene assay, we provide evidence that at least two kappaB sites in the 5'-flanking region of the rat COX II gene are involved for silica-induced transcriptional control of the COX II gene. The first motif, -404 GGGGATTCCC -395, is absolutely conserved in sequence and is localized in a similar position among the COX II genes found in humans, rats, and mice. The second motif, -91 GGGGAAAGCC -82, was conserved only in the mouse and rat COX II genes in sequence and in location. Aspirin, a COX inhibitor, was shown to suppress silica-induced NF-kappaB activation. However, prostaglandin E2, one of the important downstream reaction products catalyzed by the COX enzyme, was also shown to attenuate silica-induced NF-kappaB activation by retarding the degradation of silica-induced inhibitor NF-kappaB. These results suggest that an interdependent regulation may exist between NF-kappaB activation and COX or its products.
Genetic-factors; Gene-mutation; Silica-dusts; Quartz-dust; Carcinogens; Laboratory-animals; Animal-studies; Alveolar-cells; Author Keywords: alveolar macrophage cell line; transcription factor; inflammation; nuclear factor-kappaB
Fei Chen, Departments of 1Pathology and 2Microbiology and Immunology, The Pennsylvania State University Collage of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033
Issue of Publication
American Journal of Physiology: Lung Cellular and Molecular Physiology
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division