Expression of interleukin-6 is suppressed by inhibition of voltage-sensitive Na+/Ca2+ channels after cerebral ischemia.
Expression of interleukin-6 (IL-6), a neurotrophic cytokine, is up-regulated after cerebral ischemia, but the underlying mechanism of the up-regulation remains unclear. NS-7 is a novel blocker of voltage-sensitive Ca2+ and Na+ channels and is known to reduce cerebral damage by ischemia. The present study was undertaken to examine the association between increases in intracellular Ca2+ concentration induced by membrane depolarization and IL-6 induction. IL-6 expression in rat brain was investigated by immunohistochemistry and Western blot analysis following 3.5-48 h of reperfusion after 1.5 h of occlusion of the middle cerebral artery. NS-7 (1 mg/kg; NS-7 group) or saline (saline group) was injected i.v. 5 min after the start of reperfusion. The saline group showed clear IL-6 expression in various cortical regions, which peaked at 24 h of reperfusion. By contrast, IL-6 expression was significantly suppressed in the NS-7 group throughout the reperfusion period. Microglia activation was also reduced in the NS-7 group. These findings suggest that IL-6 expression may be up-regulated by the increased intracellular Ca2+ concentration triggered by membrane depolarization after cerebral ischemia.
Suzuki
S
S
Department of Neurology, School of Medicine, Keio University, Tokyo, Japan.
Tanaka
K
K
Nogawa
S
S
Dembo
T
T
Kosakai
A
A
Fukuuchi
Y
Y
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
C106144:4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride; D015220:Calcium Channels; D015850:Interleukin-6; D018696:Neuroprotective Agents; D011743:Pyrimidines; D015222:Sodium Channels