IDEHU   05542
INSTITUTO DE ESTUDIOS DE LA INMUNIDAD HUMORAL PROF. RICARDO A. MARGNI
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
BRUCELLA ABORTUS INDUCES COLLAGEN DEPOSITION AND MMP-9 DOWN-MODULATION IN HEPATIC STELLATE CELLS VIA TGF-β1 PRODUCTION THROUGH A MECHANISM THAT IS DEPENDENT ON A FUNCTIONAL TYPE IV SECRETION SYSTEM AND ITS EFFECTOR PROTEIN BPE005
Autor/es:
ARRIOLA BENITEZ PC; HERRMAN C; FOSSATI CA; COMERCI DI,; GIAMBARTOLOMEI GH; DELPINO MV
Lugar:
Los Cocos, Córdoba
Reunión:
Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
The liver is frequently
affected in patients with active brucellosis. Previously, we demonstrated that B.
abortus (Ba) inhibits the basal levels of MMP-9 secretion and induces
collagen deposition and TIMP-1 secretion by hepatic stellate cells (LX-2).
These phenomena were dependent on TGF-β1 induction. Since the type IV secretion system (virB) from Ba has been
involved in the modulation of immune responses during infection, we decided to
investigate whether the effect of Ba infection on LX-2 is dependent on a
functional virB system and/or its putative secreted proteins (BPE123, BPE275
and BPE005). To this end, LX-2 were infected with Ba or its isogenic mutants.
MMPs production was determined by gelatin zymography, collagen deposition by
Sirius red staining and TGF-β1 secretion by ELISA. Our results indicated that virB or the BPE005
mutant were unable to inhibit MMP-9 secretion, concomitant collagen deposition
and TGF-β1
induction, indicating that the mechanisms described involved the presence of a
functional virB secretion system and the secretion of the BPE005 protein. Since
BPE005 has homology with cyclic AMP binding proteins we attempt to revert its
role by using butiril-cAMP. All phenomena were dependent on cAMP since they
were reverted when we performed the infection with Ba in the presence of
butiril-cAMP. We also determine the rol of PKA in the signaling pathway by
using the inhibitor KT5720. Our results indicated that the PKA signaling
pathway is also involved in the described phenomena on LX-2. The importance of
this finding it that BPE005 could be the first reported effector with a
proposed function for B. abortus. All together, these results indicate
that Ba inhibit MMP-9 secretion inducing concomitant collagen deposition and
TGF-β1
secretion in a way that involved a functional virB secretion system and the
secreted protein BPE005 through a mechanisms that involved cAMP and PKA
signaling pathway.