title: Potential role of fibroblast-like synoviocytes in joint damage induced by Brucella abortus infection through production and induction of matrix metalloproteinases.
abstract: 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-α)-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.
authors: IDEHU, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4to. Piso, 1113 Buenos Aires, Argentina.
authors: Romina
authors: R
authors: Scian
authors: Paula
authors: P
authors: Barrionuevo
authors: Guillermo H
authors: GH
authors: Giambartolomei
authors: Emilio A
authors: EA
authors: De Simone
authors: Silvia I
authors: SI
authors: Vanzulli
authors: Carlos A
authors: CA
authors: Fossati
authors: Pablo C
authors: PC
authors: Baldi
authors: M Victoria
authors: MV
authors: Delpino
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001170:Arthritis, Infectious / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D002003:Brucella abortus / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D002006:Brucellosis / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007596:Joints / Q000382:microbiology* / Q000473:pathology*; D007719:Knee Joint / Q000382:microbiology; D008074:Lipoproteins / Q000276:immunology; D008213:Lymphocyte Activation; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D008074:Lipoproteins; C097319:OMP19 protein, Brucella abortus; D051195:Toll-Like Receptor 2; D020782:Matrix Metalloproteinases