PMID- 21730088
OWN - NLM
STAT- MEDLINE
DCOM- 20111021
LR  - 20211020
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 79
IP  - 9
DP  - 2011 Sep
TI  - Potential role of fibroblast-like synoviocytes in joint damage induced by 
      Brucella abortus infection through production and induction of matrix 
      metalloproteinases.
PG  - 3619-32
LID - 10.1128/IAI.05408-11 [doi]
AB  - 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-alpha)-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.
FAU - Scian, Romina
AU  - Scian R
AD  - IDEHU, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Junin 956 
      4to. Piso, 1113 Buenos Aires, Argentina.
FAU - Barrionuevo, Paula
AU  - Barrionuevo P
FAU - Giambartolomei, Guillermo H
AU  - Giambartolomei GH
FAU - De Simone, Emilio A
AU  - De Simone EA
FAU - Vanzulli, Silvia I
AU  - Vanzulli SI
FAU - Fossati, Carlos A
AU  - Fossati CA
FAU - Baldi, Pablo C
AU  - Baldi PC
FAU - Delpino, M Victoria
AU  - Delpino MV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110705
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Outer Membrane Proteins)
RN  - 0 (Chemokines)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (Lipoproteins)
RN  - 0 (OMP19 protein, Brucella abortus)
RN  - 0 (Toll-Like Receptor 2)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Antigens, Bacterial/immunology
MH  - Arthritis, Infectious/enzymology/*immunology/microbiology/pathology
MH  - Bacterial Outer Membrane Proteins/immunology
MH  - Brucella abortus/growth & development/*immunology/pathogenicity
MH  - Brucellosis/enzymology/*immunology/microbiology/pathology
MH  - Cell Line
MH  - Cell Movement/drug effects
MH  - Chemokines/biosynthesis
MH  - Culture Media, Conditioned
MH  - Cytokines/biosynthesis/metabolism
MH  - Enzyme Induction
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Joints/*microbiology/*pathology
MH  - Knee Joint/microbiology
MH  - Lipoproteins/immunology
MH  - Lymphocyte Activation
MH  - Matrix Metalloproteinases/*biosynthesis/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Monocytes/physiology
MH  - Neutrophils/physiology
MH  - Synovial Membrane/cytology/*immunology/microbiology
MH  - Toll-Like Receptor 2/metabolism
PMC - PMC3165475
EDAT- 2011/07/07 06:00
MHDA- 2011/10/22 06:00
PMCR- 2012/03/01
CRDT- 2011/07/07 06:00
PHST- 2011/07/07 06:00 [entrez]
PHST- 2011/07/07 06:00 [pubmed]
PHST- 2011/10/22 06:00 [medline]
PHST- 2012/03/01 00:00 [pmc-release]
AID - IAI.05408-11 [pii]
AID - 5408-11 [pii]
AID - 10.1128/IAI.05408-11 [doi]
PST - ppublish
SO  - Infect Immun. 2011 Sep;79(9):3619-32. doi: 10.1128/IAI.05408-11. Epub 2011 Jul 5.