Depolarization and a NO-donor stimulate interleukin-1beta release from the rat hypothalamus via a mechanism involving caspase 1.
Previous in vitro studies showed that rat hypothalamic explants release interleukin-1beta (IL-1beta); such release is significantly increased by several stimuli including 56 mM KCl and NO-donors in 20-min experiments. Here we tested the hypothesis that the above stimuli act via a mechanism involving cleavage of the IL-1beta precursor by interleukin-1beta converting enzyme (ICE, also referred to as caspase-1). A cell-permeable form of the caspase-1 inhibitor I and two different stimuli, 56 mM KCl and sodium nitroprusside (SNP), were used. The inhibitor was able to counteract the increase in IL-1beta release induced by both K+ and SNP, while having no effect on basal release.
Tringali
G
G
Institute of Pharmacology, Catholic University Medical School, Rome, Italy.
Dello Russo
C
C
Vairano
M
M
Preziosi
P
P
Navarra
P
P
D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D061945:Caspase Inhibitors; D007375:Interleukin-1; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D011189:Potassium Chloride; D007770:L-Lactate Dehydrogenase; D020170:Caspase 1