Small heat shock proteins associated with cerebral amyloid angiopathy of hereditary cerebral hemorrhage with amyloidosis (Dutch type) induce interleukin-6 secretion.
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-beta protein (A beta) 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 A beta 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 A beta were inactive, suggesting that sHsps may be among the key mediators of the local inflammatory response associated with HCHWA-D and AD lesions.
Wilhelmus
Micha M M
MM
Department of Neurology and Alzheimer Centre, Radboud University Nijmegen Medical Centre, The Netherlands.
Boelens
Wilbert C
WC
Kox
Matthijs
M
Maat-Schieman
Marion L C
ML
Veerhuis
Rob
R
de Waal
Robert M W
RM
Verbeek
Marcel M
MM
D028243:Cerebral Amyloid Angiopathy, Familial / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D006360:Heat-Shock Proteins; D015850:Interleukin-6