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

Fei Chen, Shaocong Sun, Douglas C. Kuhn, Lesley J. Gaydos, Xianglin Shi, Yongju Lu, Laurence Demers

Research output: Contribution to journalArticle

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Abstract

The role of nuclear factor (NF)-κB 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-κB can be activated in this cell line by silica exposure. Suppression of NF-κB 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 κB 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-κB activation. However, prostaglandin E 2 , one of the important downstream reaction products catalyzed by the COX enzyme, was also shown to attenuate silica-induced NF-κB activation by retarding the degradation of silica-induced inhibitor NF-κB. These results suggest that an interdependent regulation may exist between NF-κB activation and COX or its products.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume272
Issue number4 16-4
StatePublished - Apr 1 1997

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Alveolar Macrophages
Prostaglandin-Endoperoxide Synthases
Silicon Dioxide
Gene Expression
Genes
Alveolar Epithelial Cells
Cell Line
Cyclooxygenase Inhibitors
Conserved Sequence
5' Flanking Region
Electrophoretic Mobility Shift Assay
Prostaglandins E
Reporter Genes
Aspirin
Transcription Factors
Messenger RNA
Enzymes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Chen, Fei ; Sun, Shaocong ; Kuhn, Douglas C. ; Gaydos, Lesley J. ; Shi, Xianglin ; Lu, Yongju ; Demers, Laurence. / Involvement of NF-κB in silica-induced cyclooxygenase II gene expression in rat alveolar macrophages. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1997 ; Vol. 272, No. 4 16-4.
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abstract = "The role of nuclear factor (NF)-κB 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-κB can be activated in this cell line by silica exposure. Suppression of NF-κB 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 κB 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-κB activation. However, prostaglandin E 2 , one of the important downstream reaction products catalyzed by the COX enzyme, was also shown to attenuate silica-induced NF-κB activation by retarding the degradation of silica-induced inhibitor NF-κB. These results suggest that an interdependent regulation may exist between NF-κB activation and COX or its products.",
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Involvement of NF-κB in silica-induced cyclooxygenase II gene expression in rat alveolar macrophages. / Chen, Fei; Sun, Shaocong; Kuhn, Douglas C.; Gaydos, Lesley J.; Shi, Xianglin; Lu, Yongju; Demers, Laurence.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 272, No. 4 16-4, 01.04.1997.

Research output: Contribution to journalArticle

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AU - Chen, Fei

AU - Sun, Shaocong

AU - Kuhn, Douglas C.

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AU - Shi, Xianglin

AU - Lu, Yongju

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N2 - The role of nuclear factor (NF)-κB 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-κB can be activated in this cell line by silica exposure. Suppression of NF-κB 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 κB 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-κB activation. However, prostaglandin E 2 , one of the important downstream reaction products catalyzed by the COX enzyme, was also shown to attenuate silica-induced NF-κB activation by retarding the degradation of silica-induced inhibitor NF-κB. These results suggest that an interdependent regulation may exist between NF-κB activation and COX or its products.

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