Distinct modulation of microglial amyloid [beta] phagocytosis and migration by neuropeptides.sup.i.sup

Microglial activation plays an integral role in the development and course of neurodegeneration. Although neuropeptides such as bradykinin (BK), somatostatin (SST), and endothelin (ET) are known to be important mediators of inflammation in the periphery, evidence of a similar function in brain is sc...

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Published inJournal of neuroinflammation Vol. 7; p. 61
Main Authors Fleisher-Berkovich, Sigal, Filipovich-Rimon, Talia, Ben-Shmuel, Sarit, Hülsmann, Claudia, Kummer, Markus P, Heneka, Michael T
Format Journal Article
LanguageEnglish
Published BioMed Central Ltd 11.10.2010
Subjects
Bradykinin
Care and treatment
Inflammation
Neuropeptides
Phagocytosis
Physiological aspects
Germany
Israel
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Summary:Microglial activation plays an integral role in the development and course of neurodegeneration. Although neuropeptides such as bradykinin (BK), somatostatin (SST), and endothelin (ET) are known to be important mediators of inflammation in the periphery, evidence of a similar function in brain is scarce. Using immunocytochemistry, we demonstrate the expression of receptors for BK (B1, B2 subtypes), ET (ETA, ETB subtypes) and SST (SST 2, 3, 4 subtypes) in primary microglia and microglial cell lines. Exposure of BV2 and N9, as well as primary microglial cells to BK or SST increased A[beta] uptake in a concentration-dependent manner, whereas endothelin decreased A[beta] uptake. This was caused by increased phagocytosis of A[beta] since the rate of intracellular A[beta] degradation remained unaffected. All neuropeptides increased chemotactic activity of microglia. In addition, BK reduced A[beta]-induced expression of proinflammatory genes including iNOS and COX-2. ET decreased the A[beta]-induced expression of monocyte chemoattractant protein 1 and interleukin-6. These results suggest that neuropeptides play an important role in chemotaxis and A[beta] clearance and modulate the brain's response to neuroinflammatory processes.
ISSN:1742-2094
1742-2094
DOI:10.1186/1742-2094-7-61