Suppression of oxidative neuronal damage after transient middle cerebral artery occlusion in mice lacking interleukin-1.
Interleukin-1 (IL-1) contributes to ischemic neurodegeneration. However, the mechanisms regulating action of IL-1 are still poorly understood. In order to clear this central issue, mice that were gene deficient in IL-1alpha and beta (IL-1 KO) and wild-type mice were subjected to 1-h transient middle cerebral artery occlusion (tMCAO). Expression levels of IL-1beta and IL-1 receptor I (IL-1RI) were then examined. Generation of peroxynitrite and the expression of mRNAs for nitric oxide synthase (NOS) subtypes were also determined. Immunostaining for IL-1beta was increased from 6 h and peaked at 24 h after tMCAO in the microglia and macrophage. The immunoreactivities of IL-1RI were increased progressively in the microvasculature and neuron-like cells of the ipsilateral hemisphere. Infarct volumes were significantly lower in IL-1 KO mice compared with wild-type mice 48 h after tMCAO (P<0.01). The immunoreactivities of 3-nitro-L-tyrosine were determined in the neurons and microvasculature 24 h after tMCAO and were significantly decreased in the IL-1 KO mice compared to wild-type mice. In addition, expression levels of NOS mRNA in IL-1 KO mice were lower than that measured in wild-type mice. These results indicate that IL-1 is up-regulated and may play a role in neurodegeneration by peroxynitrite production during ischemia.
Ohtaki
Hirokazu
H
Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, 142-8555, Tokyo, Japan.
Funahashi
Hisayuki
H
Dohi
Kenji
K
Oguro
Takiko
T
Horai
Reiko
R
Asano
Masahide
M
Iwakura
Yoichiro
Y
Yin
Li
L
Matsunaga
Masaji
M
Goto
Noboru
N
Shioda
Seiji
S
D000818:Animals; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*
D007375:Interleukin-1; D019001:Nitric Oxide Synthase