Involvement of NF-kappaB in silica-induced cyclooxygenase II gene expression in rat alveolar macrophages.
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.
Chen
F
F
Department of Pathology, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, 17033, USA.
Sun
S
S
Kuhn
D C
DC
Gaydos
L J
LJ
Shi
X
X
Lu
Y
Y
Demers
L M
LM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002460:Cell Line; D015232:Dinoprostone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D007527:Isoenzymes / Q000235:genetics*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D051381:Rats; D012822:Silicon Dioxide / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D016328:NF-kappa B; D012822:Silicon Dioxide; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001241:Aspirin