Expression of interleukin-1beta, interleukin-1 receptor, and interleukin-1 receptor antagonist mRNA in rat carotid artery after balloon angioplasty.
Interleukin-1beta (IL-1beta) is a pleiotropic cytokine capable of inducing smooth muscle activation and leukocyte recruitment in restenosis and atherosclerosis. Our present study investigated the expression of IL-1beta, IL-1 receptor antagonist (IL-1ra), and IL-1 receptor (IL-1RI and IL-1RII) mRNA in carotid artery after balloon angioplasty using semiquantitative reverse transcription/polymerase chain reaction (RT/PCR) and Northern analysis. Time course studies revealed that IL-1beta mRNA was rapidly induced at 6 h (30-fold increase over control, P < 0.001) post balloon injury and diminished to basal levels at 24 h. The increased expression of IL-1ra mRNA was delayed, reaching a peak at 24 h (400-fold increase, P < 0.001) and sustained up to 14 days. The expression of IL-1RII mRNA was remarkably similar to that of IL-1beta, whereas the IL-1RI (the signaling receptor) mRNA expression was delayed (significantly induced at day 1; 14.2-fold increase, P < 0.01) post balloon injury. Immunohistochemical studies revealed a strong induction of IL-1beta in the area with actively proliferating and migrating smooth muscle cells (i.e., in the inner medial layer at day 1 and in neointima at day 14 after balloon injury). The differential but concomitant expression of IL-1beta, IL-1ra, IL-1RI, and IL-1RII mRNAs after balloon angioplasty suggests that each of these IL-1 system components may play a distinct role in neointima formation.
Wang
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X
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. xinkang.wang@dupontpharma.com
Romanic
A M
AM
Yue
T L
TL
Feuerstein
G Z
GZ
Ohlstein
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EH
D000800:Angioplasty, Balloon; D000818:Animals; D015152:Blotting, Northern; D002339:Carotid Arteries / Q000378:metabolism*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1