IDEHU   05542
INSTITUTO DE ESTUDIOS DE LA INMUNIDAD HUMORAL PROF. RICARDO A. MARGNI
Unidad Ejecutora - UE
artículos
Título:
Potential Role of Fibroblast-Like Synoviocytes in Joint Damage Induced by Brucella abortus Infection through 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,
Revista:
INFECTION AND IMMUNITY
Editorial:
AMER SOC MICROBIOLOGY
Referencias:
Año: 2011
ISSN:
0019-9567
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
the 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 (interleukin-6
[IL-6], IL-8, monocyte chemotactic protein 1 [MCP-1], and
granulocyte-macrophage colony-stimulating factor [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 tumor necrosis factor
alpha (TNF-_)-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 the recognition of B. abortus antigens through Toll-like
receptor 2. The intra-articular injection of HKBA or L-Omp19 into the knee
joint of mice resulted in the local induction of the 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.