Senile amyloid plaques are one of the main hallmarks of
Alzheimer’s disease (AD). They correspond to insoluble deposits of amyloid-β
peptides (Aβ) and are responsible for the inflammatory response and
neurodegeneration that lead to loss of memory. Recent data suggest that Aβ
possess antimicrobial and anti-viral activity in vitro. Here, we have used
cocultures of neuroglioma (H4) and glioblastoma (U118-MG) cells as a minimal in
vitro model to investigate whether Aβ is produced by neuroglioma cells and whether
this could result in protective anti-viral activity against HSV-1 infection.
Results showed that H4 cells secreted Aβ 42 in response to HSV-1 challenge and
that U118-MG cells could rapidly internalize Aβ 42. Production of
pro-inflammatory cytokines TNFα and IL-1β by H4 and U118-MG cells occurred
under basal conditions but infection of the cells with HSV-1 did not
significantly upregulate production. Both cell lines produced low levels of
IFNα. However, extraneous Aβ 42 induced strong production of these cytokines. A
combination of Aβ 42 and HSV-1 induced production of pro-inflammatory cytokines
TNFα and IL-1β, and IFNα in the cell lines. The reported anti-viral protection
of Aβ 42 was revealed in transfer experiments involving conditioned medium (CM)
of HSV-1-infected H4 cells. CM conferred Aβ-dependent protection against HSV-1
replication in de novo cultures of H4 cells challenged with HSV-1. Type 1
interferons did not play a role in these assays. Our data established that H4
neuroglioma cells produced Aβ 42 in response to HSV-1 infection thus inhibiting
secondary replication. This mechanism may play a role in the etiology of AD.
No comments:
Post a Comment