title: Interleukin-1 receptor and receptor antagonist gene expression after focal stroke in rats.
abstract: OBJECTIVE
  The expression of interleukin-1 beta (IL-1 beta) is upregulated after focal brain ischemia, and previous work has demonstrated its involvement in ischemic injury. The IL-1 receptor antagonist (IL-1ra), a natural competitive antagonist of IL-1 receptors (IL-1Rs), has been demonstrated to play a role in attenuating brain ischemic injury. To hypothesize the involvement of the IL-1 system in ischemic injury, we examined other IL-1 components, including IL-1ra, IL-1RI, and IL-1RII for their mRNA expression after focal stroke.
  
  
  METHODS
  Quantitative reverse transcription and polymerase chain reaction (RT-PCR) technique was used to examine the mRNA expression profile of IL-1ra and two IL-1R isoforms in a temporal fashion (n = 4 for each time point) after permanent occlusion of the middle cerebral artery (MCAO) in spontaneously hypertensive rats. IL-1ra and IL-1R mRNA expression was confirmed by Northern blot analysis using poly(A) RNA isolated after 2 and 12 hours of MCAO.
  
  
  RESULTS
  Very low levels of IL-1ra mRNA were detected in sham-operated or nonischemic cortex. IL-1ra mRNA in ischemic cortex was greatly increased at 12 hours (16.5-fold increase over sham samples, P < .001) and remained elevated for up to 5 days (17.2-fold increase, P < .01) after MCAO. IL-1RI mRNA was relatively highly expressed in normal cortex and was further elevated late after ischemic injury (3.3-fold increase at day 5, P < .001). In contrast, the low basal expression of IL-1RII mRNA was remarkably elevated at 6 hours (5.3-fold increase, P < .05), reaching peak levels 12 hours (10.3-fold increase, P < .001) after MCAO.
  
  
  CONCLUSIONS
  Differential expression of IL-1 beta, IL-1ra, IL-1RI, and IL-1RII mRNAs after focal stroke may suggest a distinct role(s) for each component of the IL-1 system in ischemic injury. The data also stress the importance of evaluating all the components of a given cytokine system (eg, agonist, receptors, and natural antagonist) after focal stroke.
authors.affiliation: Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa 19406, USA. xinkang-wang-1@sbphrd.com
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: F C
authors.initials: FC
authors.lastname: Barone
authors.forename: N V
authors.initials: NV
authors.lastname: Aiyar
authors.forename: G Z
authors.initials: GZ
authors.lastname: Feuerstein
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D002536:Cerebral Arteries; D002540:Cerebral Cortex / Q000276:immunology* / Q000378:metabolism; D017931:DNA Primers; D053590:Interleukin 1 Receptor Antagonist Protein; D002546:Ischemic Attack, Transient / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis*; D012016:Reference Values; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D053590:Interleukin 1 Receptor Antagonist Protein; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins