TY - JOUR
T1 - Activation of cultured astrocytes by amphotericin B
T2 - Stimulation of NO and cytokines production and changes in neurotrophic factors production
AU - Motoyoshi-Yamashiro, Akiko
AU - Tamura, Mizuho
AU - Moriyama, Mitsuaki
AU - Takano, Katsura
AU - Kawabe, Kenji
AU - Nakajima, Hidemitsu
AU - Katoh-Semba, Ritsuko
AU - Furuichi, Teiichi
AU - Nakamura, Yoichi
N1 - Funding Information:
This work was supported in part by a grant from the Smoking Research Foundation to Y.N. and by Grants in Aid for Scientific Research to Y.N., 24621008 and to M.M., 23580408 from the Ministry of Education, Science and Culture of Japan.
PY - 2013
Y1 - 2013
N2 - Amphotericin B (AmB) is a polyene antibiotic and reported to be one of a few reagents having therapeutic effects on prion diseases, such as the delay in the appearing of the clinical signs and the prolongation of the survival time. In prion diseases, glial cells have been suggested to play important roles by proliferating and producing various factors such as nitric oxide, proinflammatory cytokines, and neurotrophic factors. However, the therapeutic mechanism of AmB on prion diseases remains elusive.We have previously reported that AmB changed the expression of neurotoxic and neurotrophic factors in microglia (Motoyoshi et al., 2008, Neurochem. Int. 52, 1290-1296). In the present study, we examined the effects of AmB on cellular functions of rat cultured astrocytes. We found that AmB could activate astrocytes to produce nitric oxide via inducible nitric oxide synthase induction. AmB also induced mRNA expression of interleukin-1β and tumor necrosis factor-a, and productions of their proteins in astrocytes. Moreover, AmB changed levels of neurotrophic factor mRNAs and proteins. Among three neurotrophic factors examined here, neurotrophin-3 mRNA expression and its protein production in the cells were down-regulated by AmB stimulation. On the other hand, AmB significantly enhanced the amounts of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor proteins in the cells and the medium. These results suggest that AmB might show therapeutic effects on prion diseases by controlling the expression and production of such mediators in astrocytes.
AB - Amphotericin B (AmB) is a polyene antibiotic and reported to be one of a few reagents having therapeutic effects on prion diseases, such as the delay in the appearing of the clinical signs and the prolongation of the survival time. In prion diseases, glial cells have been suggested to play important roles by proliferating and producing various factors such as nitric oxide, proinflammatory cytokines, and neurotrophic factors. However, the therapeutic mechanism of AmB on prion diseases remains elusive.We have previously reported that AmB changed the expression of neurotoxic and neurotrophic factors in microglia (Motoyoshi et al., 2008, Neurochem. Int. 52, 1290-1296). In the present study, we examined the effects of AmB on cellular functions of rat cultured astrocytes. We found that AmB could activate astrocytes to produce nitric oxide via inducible nitric oxide synthase induction. AmB also induced mRNA expression of interleukin-1β and tumor necrosis factor-a, and productions of their proteins in astrocytes. Moreover, AmB changed levels of neurotrophic factor mRNAs and proteins. Among three neurotrophic factors examined here, neurotrophin-3 mRNA expression and its protein production in the cells were down-regulated by AmB stimulation. On the other hand, AmB significantly enhanced the amounts of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor proteins in the cells and the medium. These results suggest that AmB might show therapeutic effects on prion diseases by controlling the expression and production of such mediators in astrocytes.
KW - Amphotericin B
KW - Astrocytes
KW - NO
KW - Neurotrophic factors
KW - Proinflammatory cytokines
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U2 - 10.1016/j.neuint.2013.05.007
DO - 10.1016/j.neuint.2013.05.007
M3 - Article
C2 - 23727061
AN - SCOPUS:84884877344
VL - 63
SP - 93
EP - 100
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
IS - 2
ER -