Involvement of NF-kappaB in silica-induced cyclooxygenase II gene expression in rat alveolar macrophages

• Published in: The American journal of physiology Vol. 272; no. 4 Pt 1; pp. L779 - L786
• Main Authors: Chen, F, Sun, S, Kuhn, D C, Gaydos, L J, Shi, X, Lu, Y, Demers, L M
• Format: Journal Article
• Language: English
• Published: United States 01-04-1997
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Aspirin - pharmacology; Cell Line; Dinoprostone - pharmacology; Gene Expression - drug effects; Isoenzymes - genetics; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - physiology; NF-kappa B - physiology; Prostaglandin-Endoperoxide Synthases - genetics; Rats; Silicon Dioxide - pharmacology
• ISSN: 0002-9513
• DOI: 10.1152/ajplung.1997.272.4.L779

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.