IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
artículos
Título:
Immunomodulatory activity of an anti-HSV-1 synthetic stigmastane analog
Autor/es:
MICHELINI F.M.; ZORRILLA, P.; ROBELLO, CARLOS; ALCHÉ L.E.
Revista:
BIOORGANIC & MEDICINAL CHEMISTRY.
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam; Año: 2013 vol. 21 p. 560 - 568
ISSN:
0968-0896
Resumen:
Many viral infections are associated with the development of immunopathologies and autoimmune diseases,
which are of difficult treatment and for which no vaccines are yet available. Obtaining compounds
that conjugate both antiviral and immunomodulatory activities in the same molecule would be very useful
for the prevention and/or treatment of these immunopathologies.
The compound (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound 1) displays anti-Herpes
simplex virus type 1 activity in vitro and reduces the incidence of herpetic stromal keratitis (HSK) in mice,
a chronic inflammatory syndrome induced by ocular HSV-1 infection.
In the present study, compound 1 showed opposite immunomodulatory properties in vitro. It induced
the release of pro-inflammatory cytokines in HSV-1-infected epithelial cells of ocular origin, and significantly
reduced the production of these cytokines in LPS-activated macrophages. RNA microarrays
revealed various overexpressed and repressed genes in compound 1 treated infected epithelial cells
and activated macrophages, many of which are associated with innate immune responses and inflammatory
processes. These immunomodulatory properties of compound 1, together with its previously
reported antiviral activity, make it a potential drug for the treatment of HSK and many other immunopathologies
of viral and non-viral origin.