Amyloid beta peptide 1–40 enhances the action of Toll‐like receptor‐2 and ‐4 agonists but antagonizes Toll‐like receptor‐9‐induced inflammation in primary mouse microglial cell cultures

Journal of Neurochemistry - Tập 94 Số 2 - Trang 289-298 - 2005
Miriam Lotz1,2, Sandra Ebert1,2, Hermann Esselmann3, Asparouh I. Iliev4, Marco Prinz5, Nicole Wiazewicz1, Jens Wiltfang6, Joachim Gerber1, Roland Nau1
1†Department of Neurology, Georg-August-University, Göttingen, Germany;
2Miriam Lotz and Sandra Ebert contributed equally to this work.
3Department of Psychiatry, Georg-August-University, Göttingen, Germany
4Cell Biophysics Group, European Neuroscience Institute-Göttingen, Göttingen, Germany
5Department of Neuropathology, Georg-August-University, Göttingen, Germany
6Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany

Tóm tắt

AbstractThe interaction of endogenous and exogenous stimulators of innate immunity was examined in primary cultures of mouse microglial cells and macrophages after application of defined Toll‐like receptor (TLR) agonists [lipopolysaccharide (LPS) (TLR4), the synthetic lipopeptide Pam3Cys‐Ser‐Lys4 (Pam3Cys) (TLR2) and single‐stranded unmethylated CpG‐DNA (CpG) (TLR9)] alone and in combination with amyloid beta peptide (Abeta) 1–40. Abeta 1–40 stimulated microglial cells and macrophages primed by interferon‐γ in a dose‐dependent manner. Co‐administration of Abeta1–40 with LPS or Pam3Cys led to an additive release of nitric oxide (NO) and tumour necrosis factor alpha (TNF‐α). This may be one reason for the clinical deterioration frequently observed in patients with Alzheimer's disease during infections. In contrast, co‐application of Abeta1–40 with CpG led to a substantial decrease of NO and TNF‐ α release compared with stimulation with CpG alone. Abeta 1–40 and CpG did not co‐localize within the same subcellular compartment, making a direct physicochemical interaction as the cause of the observed antagonism very unlikely. This suggests that not all TLR agonists enhance the stimulatory effect of Abeta on innate immunity.

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Journal of Neurochemistry

Tập 94 Số 2

289-298

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