INVESTIGADORES
FOSSATI Carlos Alberto
congresos y reuniones científicas
Título:
Potential role of fibroblast-like synoviocytes in joint damage induced by B. abortus infection through the production and induction of matrix metalloproteinases
Autor/es:
SCIAN R; BARRIONUEVO P,; GIAMBARTOLOMEI GH,; DE SIMONE EA; VANZULLI SI; FOSSATI CA; BALDI PC; DELPINO MV,
Lugar:
Buenos Aires
Reunión:
Congreso; Brucellosis 2011 International Research Conference; 2011
Resumen:
Arthritis
is one of the most common complications of human brucellosis but its pathogenic
mechanisms have
not
been elucidated. Fibroblast-like synoviocytes (FLS) are known to be central
mediators of joint damage in
inflammatory
arthritides through the production of matrix metalloproteinases (MMPs) that
degrade collagen and
of
cytokines and chemokines that mediate recruitment and activation of leukocytes.
In this study we show that
Brucella
abortus infects and replicates in human FLS (SW982 cell
line) in vitro,
and that infection results in the
production
of MMP-2 and proinflammatory mediators (IL-6, IL-8, MCP-1, GM-CSF). Culture
supernatants from
Brucella-infected
FLS induced the migration of monocytes and neutrophils in
vitro, and also induced these cells
to
secrete MMP-9 in
a GM-CSF and IL-6 dependent fashion respectively. Reciprocally, culture
supernatants from
Brucella-infected
monocytes and neutrophils induced FLS to produce MMP-2 in a TNF-a dependent
fashion.
The
secretion of proinflammatory mediators and MMP-2 by FLS did not depend on
bacterial viability since it was
also
induced by heat-killed B. abortus (HKBA)
and by a model Brucella lipoprotein
(L-Omp19). These responses
were
mediated by recognition of B. abortus antigens
through Toll-like receptor 2. Intraarticular injection of HKBA
or
L-Omp19 in the knee joint of mice resulted in the local induction of
proinflammatory mediators, MMP-2 and
MMP-9,
and in the generation of a mixed inflammatory infiltrate. These results suggest
that FLS, and phagocytes
recruited
by them to the infection focus, may be involved in joint damage during
brucellar arthritis through the
production of MMPs and
proinflammatory mediators