Small heat shock proteins associated with cerebral amyloid angiopathy of hereditary cerebral hemorrhage with amyloidosis (Dutch type) induce interleukin-6 secretion

Abstract In hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), severe cerebral amyloid angiopathy (CAA) is associated with an inflammatory reaction. Small heat shock proteins (sHsps) are molecular chaperones and association of HspB8 with CAA in HCHWA-D has been observed. Th...

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Published in:	Neurobiology of aging 2009-02, Vol.30 (2), p.229-240
Main Authors:	Wilhelmus, Micha M.M, Boelens, Wilbert C, Kox, Matthijs, Maat-Schieman, Marion L.C, Veerhuis, Rob, de Waal, Robert M.W, Verbeek, Marcel M
Format:	Article
Language:	eng
Subjects:	Alzheimer's disease Biological and medical sciences Cerebral amyloid angiopathy Cerebral Amyloid Angiopathy, Familial - metabolism Development. Senescence. Regeneration. Transplantation Female Frontal Lobe - metabolism Fundamental and applied biological sciences. Psychology Heat-Shock Proteins - metabolism Hereditary cerebral hemorrhage with amyloidosis of the Dutch type Humans Inflammation Interleukin-6 - metabolism Internal Medicine Male Medical sciences Middle Aged Neurology Small heat shock proteins Vascular diseases and vascular malformations of the nervous system Vertebrates: nervous system and sense organs
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Summary:	Abstract In hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), severe cerebral amyloid angiopathy (CAA) is associated with an inflammatory reaction. Small heat shock proteins (sHsps) are molecular chaperones and association of HspB8 with CAA in HCHWA-D has been observed. The aims of this study were to investigate (1) if other sHsps are associated with the pathological lesions in HCHWA-D brains, (2) if the amyloid-β protein (Aβ) increases production of sHsps in cultured cerebral cells and (3) if sHsps are involved in the cerebral inflammatory processes in both Alzheimer's disease (AD) and HCHWA-D. We conclude that Hsp20, HspB8 and HspB2 are present in CAA in HCHWA-D, and that Aβ did not affect cellular sHsps expression in cultured human brain pericytes and astrocytes. In addition, we demonstrated that Hsp20, HspB2 and HspB8 induced interleukin-6 production in cultured pericytes and astrocytes, which could be antagonized by dexamethasone, whereas other sHsps and Aβ were inactive, suggesting that sHsps may be among the key mediators of the local inflammatory response associated with HCHWA-D and AD lesions.
ISSN:	0197-4580 1558-1497