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Cell and Tissue Research

, 328:549 | Cite as

STAT3 and COX-2 activation in the guinea-pig brain during fever induced by the Toll-like receptor-3 agonist polyinosinic:polycytidylic acid

  • Thilo Voss
  • Stephan W. Barth
  • Christoph Rummel
  • Rüdiger Gerstberger
  • Thomas Hübschle
  • Joachim RothEmail author
Regular Article

Abstract

Intra-arterial injections of synthetic double-stranded RNA (polyinosinic:polycytidylic acid, PIPC) at a dose of 500 μg/kg evoked pronounced fever in guinea-pigs. PIPC-induced fever could be antagonized by treatment with the non-selective cyclooxygenase (COX) inhibitor diclofenac and was, in part, attenuated by the administration of the selective COX-2-inhibitor nimesulide (dose: 5 mg/kg for both COX inhibitors). We further investigated whether direct activation of brain cells during PIPC-induced fever could be demonstrated. Using radioactive in situ hybridization, we demonstrated that treatment with PIPC resulted in an upregulation of COX-2 and interleukin-1β mRNA in the guinea-pig brain. Thus, COX-2-specific hybridization signals seemed to be mainly associated with brain blood vessels. Intra-arterial injections of PIPC further induced the pronounced nuclear translocation of the transcription factor STAT3 in the endothelium of various fore- and hindbrain areas and in the meninges. In brain structures that lacked a tight blood-brain barrier, i.e. the sensory circumventricular organs (area postrema, vascular organ of laminae terminalis, subfornical organ), the astrocytes and a population of still undetermined cellular phenotype also showed marked STAT3 activation in response to PIPC. The Toll-like receptor-3 agonist PIPC therefore caused a similar activation of brain cells as that reported for other experimental models of systemic inflammation.

Keywords

Fever Systemic inflammation Toll-like receptors Cytokines Cyclooxygenase Transcription factors Guinea-pig (male) 

Notes

Acknowledgements

The skillful technical assistance of Jolanta Murgott is gratefully acknowledged.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Thilo Voss
    • 1
  • Stephan W. Barth
    • 2
  • Christoph Rummel
    • 1
  • Rüdiger Gerstberger
    • 1
  • Thomas Hübschle
    • 1
  • Joachim Roth
    • 1
    Email author
  1. 1.Institut für Veterinär-PhysiologieJustus-Liebig-Universität GiessenGiessenGermany
  2. 2.Federal Research Centre for Nutrition and FoodKarlruheGermany

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