Interleukin-1 beta enhances survival and interleukin-6 protects against MPP+ neurotoxicity in cultures of fetal rat dopaminergic neurons.
To investigate the relationships between the central nervous system and interleukins, ventral mesencephalic cells from embryonic 17-day-old rats were cultured for 3 days in vitro (DIV) and exposed to interleukin-1 beta (IL-1 beta), interleukin-3 (IL-3), or interleukin-6 (IL-6) for the following 2 or 3 DIV with or without 2 microM 1-methyl-4-phenylpyridinium (MPP+). Thus, the survival of and the MPP+ neurotoxicity against the dopaminergic neurons immunostained with anti-tyrosine hydroxylase antibody were examined. For the survival studies, IL-1 beta has been shown to have a survival-promoting effect on dopaminergic neurons. This effect is initiated at a concentration between 0.1 and 1 ng/ml. In contrast to the effect of IL-1 beta, IL-3 and IL-6 failed to increase the survival of dopaminergic neurons. In MPP+ neurotoxicity analysis, only IL-6 among the three interleukins studied here has been shown to attenuate the MPP+ neurotoxicity against dopaminergic neurons in a dose-dependent manner; this neuro-protective action is apparent at a concentration of 10 ng/ml. In addition, these three interleukins did not promote glial proliferation. These findings suggest that the effects of IL-1 beta and IL-6 on dopaminergic neurons are not mediated by glial proliferation, that IL-1 beta acts as a neurotrophic factor on dopaminergic neurons, and that IL-6 is capable of protecting dopaminergic neurons from the neurotoxicity of MPP+.
Akaneya
Y
Y
Department of Neurology, Kinki University School of Medicine, Osaka, Japan.
Takahashi
M
M
Hatanaka
H
H
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008636:Mesencephalon / Q000187:drug effects* / Q000276:immunology; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D007375:Interleukin-1; D015850:Interleukin-6; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine