Effects of Amphotericin B on the expression of neurotoxic and neurotrophic factors in cultured microglia.
Amphotericin B (AmB) is a polyene antibiotic and reported to have therapeutic effects on prion diseases, in which the microglial activation has been suggested to play important roles by proliferating and producing various factors such as nitric oxide, proinflammatory cytokines, and so on. However, the therapeutic mechanism of AmB on prion diseases remains elusive. In the present study, we investigated the effects of AmB on cellular functions of rat primary cultured microglia. We found that AmB, similarly as lipopolysaccharide (LPS), could activate microglia to produce nitric oxide via inducible nitric oxide synthase. Both AmB and LPS also induced mRNA expressions of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in microglia. AmB also changed the expression levels of neurotrophic factors mRNAs. AmB and LPS significantly down-regulated the level of ciliary neurotrophic factor mRNA. However, AmB, but not LPS, significantly up-regulated the level of glial cell-line derived neurotrophic factor mRNA in microglia. In addition, brain-derived neurotrophic factor mRNA expression level was tending upward by treatment with AmB, but not with LPS. Taken together, these results suggest that AmB regulates the microglial activation in different manner from LPS and that microglia may participate in the therapeutic effects of AmB on prion diseases by controlling the expression and production of such mediators.
Motoyoshi
Akiko
A
Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University 1-1, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Nakajima
Hidemitsu
H
Takano
Katsura
K
Moriyama
Mitsuaki
M
Kannan
Yukiko
Y
Nakamura
Yoichi
Y
D000666:Amphotericin B / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000819:agonists / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000819:agonists / Q000235:genetics; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000819:agonists / Q000235:genetics; D005911:Gliosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053583:Interleukin-1beta / Q000819:agonists / Q000235:genetics; D015850:Interleukin-6 / Q000819:agonists / Q000235:genetics; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000819:agonists / Q000235:genetics; D009498:Neurotoxins / Q000819:agonists / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D017096:Prion Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000935:Antifungal Agents; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D051100:Glial Cell Line-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D015850:Interleukin-6; D009414:Nerve Growth Factors; D009498:Neurotoxins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000666:Amphotericin B; D019001:Nitric Oxide Synthase