Massive gliosis induced by interleukin-6 suppresses Aβ deposition in vivo

Evidence against inflammation as a driving force for amyloid deposition

Paramita Chakrabarty, Karen Jansen-West, Amanda Beccard, Carolina Ceballos-Diaz, Yona Levites, Christophe Verbeeck, Abba Zubair, Dennis W Dickson, Todd E. Golde, Pritam Das

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

Proinflammatory stimuli, after amyloid β (Aβ) deposition, have been hypothesized to create a self-reinforcing positive feedback loop that increases amyloidogenic processing of the Aβ precursor protein (APP), promoting further Aβ 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 Aβ 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 Aβ 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 Aβ 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 Aβ in young Tg2576 mice. These results indicate that mIL-6-mediated reactive gliosis may be beneficial early in the disease process by potentially enhancing Aβ 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 Aβ deposition in vivo.

Original languageEnglish (US)
Pages (from-to)548-559
Number of pages12
JournalFASEB Journal
Volume24
Issue number2
DOIs
StatePublished - Feb 2010

Fingerprint

Gliosis
Amyloid
Protein Precursors
Interleukin-6
Inflammation
Processing
Brain
Alzheimer Disease
Feedback
Microglia
Pathology
Phagocytosis
Neuroglia
Up-Regulation
Cytokines

Keywords

  • Alzheimer's disease
  • APP
  • Neuroinflammation
  • Recombinant adeno-associated virus

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Chakrabarty, P., Jansen-West, K., Beccard, A., Ceballos-Diaz, C., Levites, Y., Verbeeck, C., ... Das, P. (2010). Massive gliosis induced by interleukin-6 suppresses Aβ deposition in vivo: Evidence against inflammation as a driving force for amyloid deposition. FASEB Journal, 24(2), 548-559. https://doi.org/10.1096/fj.09-141754

Massive gliosis induced by interleukin-6 suppresses Aβ deposition in vivo : Evidence against inflammation as a driving force for amyloid deposition. / Chakrabarty, Paramita; Jansen-West, Karen; Beccard, Amanda; Ceballos-Diaz, Carolina; Levites, Yona; Verbeeck, Christophe; Zubair, Abba; Dickson, Dennis W; Golde, Todd E.; Das, Pritam.

In: FASEB Journal, Vol. 24, No. 2, 02.2010, p. 548-559.

Research output: Contribution to journalArticle

Chakrabarty, P, Jansen-West, K, Beccard, A, Ceballos-Diaz, C, Levites, Y, Verbeeck, C, Zubair, A, Dickson, DW, Golde, TE & Das, P 2010, 'Massive gliosis induced by interleukin-6 suppresses Aβ deposition in vivo: Evidence against inflammation as a driving force for amyloid deposition', FASEB Journal, vol. 24, no. 2, pp. 548-559. https://doi.org/10.1096/fj.09-141754
Chakrabarty, Paramita ; Jansen-West, Karen ; Beccard, Amanda ; Ceballos-Diaz, Carolina ; Levites, Yona ; Verbeeck, Christophe ; Zubair, Abba ; Dickson, Dennis W ; Golde, Todd E. ; Das, Pritam. / Massive gliosis induced by interleukin-6 suppresses Aβ deposition in vivo : Evidence against inflammation as a driving force for amyloid deposition. In: FASEB Journal. 2010 ; Vol. 24, No. 2. pp. 548-559.
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