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
American Journal of Physiology: Lung Cellular and Molecular Physiology