Supression of Acute Experimental Inflammation by Antisense Oligonucleotides Targeting Secretory Phospholipase A2 (sPLA2)IN VITRO and IN VIVO Experiments

  • Ulrich Tibes
  • Sigrid P. Röhr
  • Werner Scheuer
  • Elke Amandi-Burgermeister
  • Anette Litters
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 469)

Summary

In HepG2 cells phosphorothioate modified antisense oligonucleotides against a sequence in the Ca2+ binding domain (AS-Ca2+) of type II sPLA2 mRNA restrained IL-6-induced synthesis of sPLA2 protein, sPLA2 mRNA (northern blot), and abolished IL-6 stimulated PGE2 release. An antisense oligonucleotide corresponding to a sequence in the catalytic domain (AS-Cat) of sPLA2 was less effective. The antisense oligonucleotides did not affect albumin synthesis in HepG2 cells, additionally demonstrating their specificity. The corresponding AS-Ca2+ against a homologous part of the rat sPLA2 mRNA depressed rat carrageenin oedema for 60–70%. Identical suppression was achieved by specific low molecular weight inhibitors of sPLA2. Since cyclo- and 5-lipoxygenase inhibitors exerted similar reductions of carrageenin oedema type II sPLA2 dependent eicosanoid formation seems to be a key cascade in this type of inflammation.

Keywords

Hydrogen Peroxide Depression Albumin Pyruvate Glutamine 

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Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Ulrich Tibes
    • 1
  • Sigrid P. Röhr
    • 1
  • Werner Scheuer
    • 2
  • Elke Amandi-Burgermeister
    • 2
  • Anette Litters
    • 1
  1. 1.Dept. of Preclinical ResearchBoehringer Mannheim GmbHMannheimGermany
  2. 2.Dept. of Molecular PharmacologyBoehringer Mannheim GmbHPenzbergGermany

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