Transcriptional Regulation of Secreted Phospholipase A2 in Human HepG2 Cells, Rat Astrocytes and Rabbit Articular Chondrocytes

  • Mouloud Ziari
  • Francis Berenbaum
  • Qishi Fan
  • Colette Salvat
  • Marie Thérèse Corvol
  • Jean Luc Olivier
  • Gilbert Bereziat
Part of the NATO ASI Series book series (NSSA, volume 266)


We studied the regulation of the release and transcriptional regulation of the secreted type II phospholipase A2 (PLA2) in rat astrocytes, rabbit articular chondrocytes and the human hepatoma cell line HepG2. The interleukins IL-1, IL-6, TNF« stimulate PLA release in these cell lines. Okadaic acid and TPA decrease the release of PLA,, by HepG2 cells which is contrary to the effect of forskolin. Synergisms between IL-1 and forskolin in rat astrocytes, IL-6 and forskolin in HepG2 cells were observed in the secretion of PLA2. The same synergisms were observed for transcriptional activity measured in CAT assays. Surprisingly IL-1 and TNF as well as okadaïc acid and TPA decrease the CAT activities induced in HepG2 cells. The transcription of the PLA2 gene in rabbit chondrocytes and rat astrocytes appears to be regulated by positive regulatory DNA elements located in the first hundred base pairs upstream to the first exon. In rabbit chondrocytes, the region [−326; −264] was found to be critical for the transcriptional activity. The regulation of the promoter in HepG2 cells seems to be more complex and results from the combination of several positive and negative regulatory elements located in the region which spans from positions −1614 to −87.


HepG2 Cell Okadaic Acid PLA2 Activity cAMP Dibutyryl Human HepG2 
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Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Mouloud Ziari
    • 1
  • Francis Berenbaum
    • 2
  • Qishi Fan
    • 1
  • Colette Salvat
    • 1
  • Marie Thérèse Corvol
    • 2
  • Jean Luc Olivier
    • 1
  • Gilbert Bereziat
    • 1
  1. 1.Laboratoire de Biochimie, CHU Saint-AntoineURA CNRS 1283Paris Cedex 12France
  2. 2.INSERM U30Hopital NeckerParis Cedex 15France

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