Abstract：
:Intra-arterial injections of synthetic double-stranded RNA (polyinosinic:polycytidylic acid, PIPC) at a dose of 500 microg/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-1 beta 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.
journal_name
Cell Tissue Resjournal_title
Cell and tissue researchauthors
Voss T,Barth SW,Rummel C,Gerstberger R,Hübschle T,Roth Jdoi
10.1007/s00441-007-0386-6subject
Has Abstractpub_date
2007-06-01 00:00:00pages
549-61issue
3eissn
0302-766Xissn
1432-0878journal_volume
328pub_type
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journal_title：Cell and tissue research
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