Heparin inhibits induction of nitric oxide synthase by cytokines in rat brain microvascular endothelial cells.
The inflammatory reaction following ischemic brain injury involves bioactive mediators released mainly from leukocytes. The aim of this in vitro-study was to evaluate possible modulatory actions of heparin on nitric oxide synthesis induced by proinflammatory cytokines. Rat microvascular brain endothelial cells were isolated from adult rat brains and treated with interferon-gamma (IFN-gamma) and interleukin-1beta (IL-1beta) with or without heparin. The expression of inducible nitric oxide synthase (iNOS) mRNA and the iNOS protein activity was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Griess reagent, respectively. Heparin in a dose-dependent manner attenuated the increase in iNOS expression and NO release after cytokine activation. Thus, in addition to its anticoagulatory effect, heparin may also be effective in the prevention of inflammatory reaction after cerebral ischemia.
Department of Neurology, University of Heidelberg, Germany.
E
E
Bonmann
E
E
Jüttler
H E
HE
Krestel
M
M
Spranger
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000201:enzymology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D007371:Interferon-gamma; D006493:Heparin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat