Motoyoshi Akiko, Nakajima Hidemitsu, Takano Katsura, Moriyama Mitsuaki, Kannan Yukiko, Nakamura Yoichi
Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University 1-1, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Neurochem Int. 2008 May;52(6):1290-6. doi: 10.1016/j.neuint.2008.01.012. Epub 2008 Feb 2.
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.
两性霉素B（AmB）是一种多烯类抗生素，据报道对朊病毒疾病具有治疗作用，其中小胶质细胞激活被认为通过增殖并产生各种因子（如一氧化氮、促炎细胞因子等）发挥重要作用。然而，AmB对朊病毒疾病的治疗机制仍不清楚。在本研究中，我们研究了AmB对大鼠原代培养小胶质细胞功能的影响。我们发现，AmB与脂多糖（LPS）类似，可通过诱导型一氧化氮合酶激活小胶质细胞以产生一氧化氮。AmB和LPS还诱导小胶质细胞中白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α的mRNA表达。AmB还改变了神经营养因子mRNA的表达水平。AmB和LPS显著下调睫状神经营养因子mRNA的水平。然而，AmB而非LPS显著上调小胶质细胞中胶质细胞源性神经营养因子mRNA的水平。此外，用AmB处理可使脑源性神经营养因子mRNA表达水平呈上升趋势，但用LPS处理则不然。综上所述，这些结果表明AmB以与LPS不同的方式调节小胶质细胞激活，并且小胶质细胞可能通过控制此类介质的表达和产生参与AmB对朊病毒疾病的治疗作用。
