| First Author | Chakrabarty P | Year | 2010 |
| Journal | FASEB J | Volume | 24 |
| Issue | 2 | Pages | 548-59 |
| PubMed ID | 19825975 | Mgi Jnum | J:156612 |
| Mgi Id | MGI:4421085 | Doi | 10.1096/fj.09-141754 |
| Citation | Chakrabarty P, et al. (2010) Massive gliosis induced by interleukin-6 suppresses Abeta deposition in vivo: evidence against inflammation as a driving force for amyloid deposition. FASEB J 24(2):548-59 |
| abstractText | Proinflammatory stimuli, after amyloid beta (Abeta) deposition, have been hypothesized to create a self-reinforcing positive feedback loop that increases amyloidogenic processing of the Abeta precursor protein (APP), promoting further Abeta accumulation and neuroinflammation in Alzheimer's disease (AD). Interleukin-6 (IL-6), a proinflammatory cytokine, has been shown to be increased in AD patients implying a pathological interaction. To assess the effects of IL-6 on Abeta deposition and APP processing in vivo, we overexpressed murine IL-6 (mIL-6) in the brains of APP transgenic TgCRND8 and TG2576 mice. mIL-6 expression resulted in extensive gliosis and concurrently attenuated Abeta deposition in TgCRND8 mouse brains. This was accompanied by up-regulation of glial phagocytic markers in vivo and resulted in enhanced microglia-mediated phagocytosis of Abeta aggregates in vitro. Further, mIL-6-induced neuroinflammation had no effect on APP processing in TgCRND8 and had no effect on APP processing or steady-state levels of Abeta in young Tg2576 mice. These results indicate that mIL-6-mediated reactive gliosis may be beneficial early in the disease process by potentially enhancing Abeta plaque clearance rather than mediating a neurotoxic feedback loop that exacerbates amyloid pathology. This is the first study that methodically dissects the contribution of mIL-6 with regard to its potential role in modulating Abeta deposition in vivo. |
