title: Upregulated expression of Toll-like receptor 4 in peripheral blood of ischaemic stroke patients correlates with cyclooxygenase 2 expression.
abstract: OBJECTIVE
  An inflammatory process following stroke in human brains and systemic inflammatory responses after stroke in humans have been reported by numerous investigators. The aim of the study was to investigate if genes involved in the cyclooxygenase 2 (COX-2) pathway are upregulated at peripheral level in patients after transient ischaemic attack (TIA) and stroke.
  
  
  METHODS
  Blood samples were obtained from two groups of patients undergoing carotid endarterectomy. The first group included 25 patients who presented TIA or ischaemic stroke. The second group included 35 patients who had an asymptomatic internal carotid artery stenosis. Total RNA was isolated and the expression of Toll-like Receptor 4 (TLR4), COX-2, membrane-associated Prostaglandin E synthase (mPGES-1), Prostaglandin E₂ receptors (EP3 and EP4) was analysed by real time RT-PCR.
  
  
  RESULTS
  Expression of COX-2 and TLR4 were significantly increased in symptomatic patients (p < 0.001). Correlation analysis showed that TLR4 expression significantly correlated with COX-2 expression (R = 0.65; p < 0.01) in ischaemic stroke patients. This correlation was not observed in TIA and asymptomatic patients.
  
  
  CONCLUSIONS
  Our results suggest that the peripheral mechanism of inflammatory injury after stroke may be mediated by TLR4 through a COX-2-dependent pathway.
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ferronato
authors.forename: M G
authors.initials: MG
authors.lastname: Lira
authors.forename: S
authors.initials: S
authors.lastname: Olivato
authors.forename: A
authors.initials: A
authors.lastname: Scuro
authors.forename: G F
authors.initials: GF
authors.lastname: Veraldi
authors.forename: M G
authors.initials: MG
authors.lastname: Romanelli
authors.forename: C
authors.initials: C
authors.lastname: Patuzzo
authors.forename: G
authors.initials: G
authors.lastname: Malerba
authors.forename: P F
authors.initials: PF
authors.lastname: Pignatti
authors.forename: S
authors.initials: S
authors.lastname: Mazzucco
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D016893:Carotid Stenosis / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000601:surgery; D051546:Cyclooxygenase 2 / Q000235:genetics*; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D007558:Italy; D008297:Male; D008875:Middle Aged; D000071876:Prostaglandin-E Synthases; D012313:RNA / Q000097:blood*; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000235:genetics; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C545647:PTGER3 protein, human; C545650:PTGER4 protein, human; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D012313:RNA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases