Borrelia burgdorferi induces matrix metalloproteinases by neural cultures

Perides, George; Tanner-Brown, Linda M.; Eskildsen, Manuel; Klempner, Mark S.

doi:10.1002/(sici)1097-4547(19991215)58:6<779::aid-jnr5>3.0.co;2-l

Cited by 40 publications

(29 citation statements)

References 67 publications

(78 reference statements)

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“…burgdorferi can also induce MMP expression by neural cells, cartilage explants, and chondrocytes (33,69). When such cells are incubated with B. burgdorferi, they express and secrete in a dose-dependent manner several MMPs, including MMP-1, MMP-3, and MMP-9, as well as proteolytic activity associated with ADAM-TS4 and ADAM-TS11 (33,53,69). Using actinomycin D to inhibit RNA transcription, we determined by reverse transcriptase PCR that MMP induction is transcriptionally regulated (69).…”

Section: Discussionmentioning

confidence: 99%

“…When such cells are incubated with B. burgdorferi, they express and secrete in a dose-dependent manner several MMPs, including MMP-1, MMP-3, and MMP-9, as well as proteolytic activity associated with ADAM-TS4 and ADAM-TS11 (33,53,69). Using actinomycin D to inhibit RNA transcription, we determined by reverse transcriptase PCR that MMP induction is transcriptionally regulated (69). To understand whether proteases play a role in penetration of the BBB, we examined the roles of plasminogen and MMPs.…”

Section: Discussionmentioning

confidence: 99%

“…Not only do these enzymes naturally occur in the blood circulation, but they are also expressed as a result of the interaction between host cells and B. burgdorferi. There have been several reports showing that astrocytes (69), chondrocytes (33,53), and monocytes (26,27) express MMPs in response to B. burgdorferi. These reports have also shown that the interaction of B. burgdorferi with host cells leads to the activation of plasminogen that activates these MMPs, thus facilitating the degradation of the extracellular matrix.…”

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confidence: 99%

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Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

Grab¹,

et al. 2005

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Neurological manifestations of Lyme disease in humans are attributed in part to penetration of the blood-brain barrier (BBB) and invasion of the central nervous system (CNS) by Borrelia burgdorferi. However, how the spirochetes cross the BBB remains an unresolved issue. We examined the traversal of B. burgdorferi across the human BBB and systemic endothelial cell barriers using in vitro model systems constructed of human brain microvascular endothelial cells (BMEC) and EA.hy 926, a human umbilical vein endothelial cell (HUVEC) line grown on Costar Transwell inserts. These studies showed that B. burgdorferi differentially crosses human BMEC and HUVEC and that the human BMEC form a barrier to traversal. During the transmigration by the spirochetes, it was found that the integrity of the endothelial cell monolayers was maintained, as assessed by transendothelial electrical resistance measurements at the end of the experimental period, and that B. burgdorferi appeared to bind human BMEC by their tips near or at cell borders, suggesting a paracellular route of transmigration. Importantly, traversal of B. burgdorferi across human BMEC induces the expression of plasminogen activators, plasminogen activator receptors, and matrix metalloproteinases. Thus, the fibrinolytic system linked by an activation cascade may lead to focal and transient degradation of tight junction proteins that allows B. burgdorferi to invade the CNS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

Grab¹,

et al. 2005

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“…Human and rat type I astrocytes expressed MMP-9 when incubated with B. burgdorferi in the same manner as primary neural cultures (30). B. burgdorferi has been demonstrated to induce the secretion and activation of MMP-9 from primary human cells, including monocytes, neutrophils, keratinocytes, and astrocytes (11).…”

Section: Discussionmentioning

confidence: 97%

CD14 Mediates Cross Talk between Mononuclear Cells and Fibroblasts for Upregulation of Matrix Metalloproteinase 9 byBorrelia burgdorferi

et al. 2007

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Lyme disease is an infection caused by a tick-borne spirochete, Borrelia burgdorferi. Matrix metalloproteinase 9 (MMP-9) was selectively upregulated in the erythema migrans skin lesions of patients with acute Lyme disease. In this study, the mechanism of upregulation of MMP-9 was investigated in vitro and in vivo. The concentrations of MMP-9 and soluble CD14 were markedly elevated in serum from patients with acute Lyme disease and were also upregulated in U937 cells by B. burgdorferi in a time-and concentration-dependent manner. MMP-9 mRNA was expressed at baseline in fibroblasts in the presence or absence of B. burgdorferi. However, when fibroblasts were incubated with supernatants from U937 cells with B. burgdorferi or recombinant CD14, the expression of MMP-9 was significantly increased. This effect was completely abolished by the anti-CD14 antibody. These data suggest that the upregulation of MMP-9 by B. burgdorferi involves the CD14 pathway in infiltrating inflammatory cells. Fibroblasts could be recruited to amplify local production of MMP-9 by acquiring CD14 from macrophages.Lyme disease is an infection caused by a tick-borne spirochete, Borrelia burgdorferi. It is the most common vector-borne disease in the United States (18, 37). The hallmark of acute Lyme disease is the characteristic skin lesions, known as erythema migrans (EM) skin lesions. Other acute clinical manifestations result from dissemination of the spirochete to the central and peripheral nervous systems, the heart, and the musculoskeletal system (7,21,36).Some bacteria that disseminate from a skin inoculation site secrete enzymes (e.g., collagenases and elastases) that are thought to participate in the spreading process by disrupting the extracellular matrix barrier (10,22,38). B. burgdorferi does not secrete any enzymes capable of digesting collagen, laminin, or gelatin (22). We have demonstrated that expression of matrix metalloproteinase 9 (MMP-9) was selectively upregulated in human EM skin lesions of acute Lyme disease. The activated fibroblasts and infiltrating mononuclear cells were the major sources of local MMP-9 production (43). Infiltration of the skin with mononuclear cells is frequently observed in EM lesions of acute Lyme disease (3). We hypothesize that bacterial induction of host proteases may play a major role in the dissemination of B. burgdorferi (43).CD14 on blood monocytes mediate monocyte/macrophage activation by lipopolysaccharide (LPS). LPS bound to CD14 may contribute to atherogenesis by stimulating macrophages to produce tumor necrosis factor alpha, interleukin 1 (IL-1), IL-6, IL-8, IL-12, alpha interferon, migration inhibitory factors, chemokines, eicosanoids, and reactive oxygen species, which in turn stimulate the production of a second wave of chemokines, cytokines, and adhesion and signaling molecules. The mature CD14 protein is present in two isoforms: membrane bound and soluble.Membrane-associated CD14 (mCD14) is expressed on myeloid cells, including tissue macrophages, monocytes, promonocytes, and activate...

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“…The acquired proteolytic activity allows B. burgdorferi and related spirochetes to degrade components of the extracellular matrix (8,18) and penetrate endothelial cell monolayers in vitro (9) and provides for efficient dissemination in mice (32,43) and ticks (7). Additionally, live B. burgdorferi induces the expression and release of matrix metalloproteinase 1 (MMP-1) and MMP-9 in inflammatory and noninflammatory human (21) and rat primary neural cells (46) in vitro. The presence of monocytic cell-derived MMPs leads to enhanced penetration of tissue barriers by B. burgdorferi in vitro (21).…”

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confidence: 99%