Differential regulation of MMP-1/9 and TIMP-1 secretion in human monocytic cells in response to Mycobacterium tuberculosis

Friedland, Jon S.; Shaw, Terry C.; Price, Nicholas; Dayer, Jean‐Michel

doi:10.1016/s0945-053x(01)00175-5

Cited by 35 publications

(33 citation statements)

References 29 publications

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“…2D). These data further confirm previous studies that show that THP-1 cells are an appropriate monocyte model in which to study MMP-9 activity in models of TB (17)(18)(19)(20)31). The addition of CoMTB to monocytic cells had a dose-dependent effect on MMP-9 secretion (Fig.…”

Section: Monocyte-monocyte Network Stimulate Mmp-9 But Not Timp-1 supporting

confidence: 91%

“…Furthermore, elevated MMP-9 activity (but not TIMP-1 levels) was found in cerebrospinal fluid from patients with tuberculous meningitis and was related to fatal outcome and cerebral injury (17). The fact that the signaling pathways regulating MMP-1/9 and TIMP-1 secretion are distinct in monocytic cells infected with M. tb, is a further indication of differential regulation of this enzyme and its principal inhibitor (19).…”

Section: T Uberculosis (Tb)mentioning

confidence: 99%

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Unopposed Matrix Metalloproteinase-9 Expression in Human Tuberculous Granuloma and the Role of TNF-α-Dependent Monocyte Networks

Price

Gilman

Uddin

et al. 2003

The Journal of Immunology

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Tuberculosis is characterized by granuloma formation and caseous necrosis, but the factors causing tissue destruction are poorly understood. Matrix metalloproteinase (MMP)-9 (92-kDa gelatinase) secretion from monocytes is stimulated by Mycobacterium tuberculosis (M. tb) and associated with local tissue injury in tuberculosis patients. We demonstrate strong immunohistochemical MMP-9 staining in monocytic cells at the center of granuloma and adjacent to caseous necrosis in M. tb-infected patient lymph nodes. Minimal tissue inhibitor of MMPs-1 staining indicated that MMP-9 activity is unopposed. Because granulomas characteristically contain few mycobacteria, we investigated whether monocyte-monocyte cytokine networks amplify MMP-9 secretion. Conditioned medium from M. tb-infected primary human monocytes or THP-1 cells (CoMTB) stimulated MMP-9 gene expression and a >10-fold increase in MMP-9 secretion by monocytes at 3–4 days (p < 0.009, vs controls). Although CoMTB stimulated dose-dependent MMP-9 secretion, MMP-1 (52-kDa collagenase) was not induced. Anti-TNF-α Ab but not IL-1R antagonist pretreatment decreased CoMTB-induced MMP-9 secretion by 50% (p = 0.0001). Anti-TNF-α Ab also inhibited MMP-9 secretion from monocytic cells by 50%, 24 h after direct M. tb infection (p = 0.0002). Conversely, TNF-α directly stimulated dose-dependent MMP-9 secretion. Pertussis toxin inhibited CoMTB-induced MMP-9 secretion and enhanced the inhibitory effect of anti-TNF-α Ab (p = 0.05). Although chemokines bind to G protein-linked receptors, CXCL8, CXCL10, CCL2, and CCL5 did not stimulate monocyte MMP-9 secretion. However, the response to cholera toxin confirmed that G protein signaling pathways were intact. In summary, MMP-9 within tuberculous granuloma is associated with tissue destruction, and TNF-α, critical for antimycobacterial granuloma formation, is a key autocrine and paracrine regulator of MMP-9 secretion.

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Section: Monocyte-monocyte Network Stimulate Mmp-9 But Not Timp-1 supporting

confidence: 91%

Section: T Uberculosis (Tb)mentioning

confidence: 99%

Unopposed Matrix Metalloproteinase-9 Expression in Human Tuberculous Granuloma and the Role of TNF-α-Dependent Monocyte Networks

Price

Gilman

Uddin

et al. 2003

The Journal of Immunology

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“…As early as the 1970s, it was shown that stimulation of guinea pig macrophages by mycobacterial extracts increases secretion of collagenase [26]. Stimulation of human THP-1 cells upregulates gene expression of MMP-1 and MMP-9 [18,20,27,28]. This upregulation could be driven by lipomannans alone and was dependent on Toll-like receptor and CD14 signalling [29].…”

Section: Defining the Mmps Involved In The Pathogenesis Of Tbmentioning

confidence: 99%

Matrix metalloproteinases in tuberculosis

Elkington¹,

Ugarte-Gil²,

Friedland³

2011

Eur Respir J

117

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Tuberculosis (TB) remains a global health pandemic. Infection is spread by the aerosol route and Mycobacterium tuberculosis must drive lung destruction to be transmitted to new hosts. Such inflammatory tissue damage is responsible for morbidity and mortality in patients. The underlying mechanisms of matrix destruction in TB remain poorly understood but consideration of the lung extracellular matrix predicts that matrix metalloproteinases (MMPs) will play a central role, owing to their unique ability to degrade fibrillar collagens and other matrix components. Since we proposed the concept of a matrix degrading phenotype in TB a decade ago, diverse data implicating MMPs as key mediators in TB pathology have accumulated. We review the lines of investigation that have indicated a critical role for MMPs in TB pathogenesis, consider regulatory pathways driving MMPs and propose that inhibition of MMP activity is a realistic goal as adjunctive therapy to limit immunopathology in TB.

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“…Once secreted and activated, the activities of MMPs are regulated by specific tissue inhibitors (TIMPs) produced by a variety of cells, TIMP-1 being a major MMP-9 inhibitor (1). Although MMP-9 is a critical factor in host defense mechanisms by facilitating leukocyte extravasation into infected sites, excessive production of MMP-9 may contribute to host tissue injury and exacerbation of the inflammation response, as reported in Mycobacterium tuberculosis infection (3,9,28,30,31).Lipomannan (LM) and lipoarabinomannan (LAM) are major complex lipoglycans ubiquitously found in the mycobacterial cell wall. LM, considered as a direct biosynthetic precursor of LAM, is composed of a phosphatidyl-myo-inositol anchor linked to a D-mannan core.…”

mentioning

confidence: 99%

Mycobacterial Lipomannan Induces Matrix Metalloproteinase-9 Expression in Human Macrophagic Cells through a Toll-Like Receptor 1 (TLR1)/TLR2- and CD14-Dependent Mechanism

et al. 2005

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Lipomannans (LM) from various mycobacterial species were found to induce expression and secretion of the matrix metalloproteinase 9 (MMP-9) both in human macrophage-like differentiated THP-1 cells and in primary human macrophages. Inhibition studies using antireceptor-neutralizing antibodies are indicative of a Toll-like receptor 1 (TLR1)/TLR2-and CD14-dependent signaling mechanism. Moreover, LM was shown to down-regulate transcription of the metalloproteinase inhibitor TIMP-1, a major endogenous MMP-9 regulator.Matrix metalloproteinases (MMPs) form a family of Zn 2ϩ -and Ca 2ϩ -dependent endopeptidases, which are involved in various physiological and pathological processes, through their capacity for degrading components of the extracellular matrix (11,32,36,37). MMP-9, known as the 92-kDa gelatinase B, is the predominant MMP secreted by monocytes/macrophages during bacterial diseases (7-9, 25, 27, 30, 31, 38). This enzyme is secreted as a proenzyme latent form, which undergoes extracellular proteolytic cleavage to provide the active form. Once secreted and activated, the activities of MMPs are regulated by specific tissue inhibitors (TIMPs) produced by a variety of cells, TIMP-1 being a major MMP-9 inhibitor (1). Although MMP-9 is a critical factor in host defense mechanisms by facilitating leukocyte extravasation into infected sites, excessive production of MMP-9 may contribute to host tissue injury and exacerbation of the inflammation response, as reported in Mycobacterium tuberculosis infection (3,9,28,30,31).Lipomannan (LM) and lipoarabinomannan (LAM) are major complex lipoglycans ubiquitously found in the mycobacterial cell wall. LM, considered as a direct biosynthetic precursor of LAM, is composed of a phosphatidyl-myo-inositol anchor linked to a D-mannan core. In LAM, the mannan domain is followed of a D-arabinan domain which can be capped by mannosyl or phosphoinositol residues (2, 16, 24). LM and LAM exhibit a wide array of biological activities which enhance antimycobacterial immune defenses or facilitate mycobacterial survival through inhibition of the immune response.The interaction of these lipoglycans with Toll-like receptor 2 (TLR2), CD14, mannose receptor or dendritic cell-specific intracellular adhesion molecule 3 is dependent on structural features of LM and LAM (4,10,19,[21][22][23]29,31,35,39). LAM from M. tuberculosis was reported to up-regulate MMP-9 expression in the monocytic THP-1 cell line and in macrophages through binding to the mannose receptor (3, 30, 31). However, although recent studies have emphasized the role of LM as a strong immunomodulator (2), no information is available regarding to its potential contribution in MMP-9 secretion.In this study, we investigated the ability of LM from various mycobacteria, including pathogenic species, to stimulate MMP-9 gene expression and MMP-9 secretion from human macrophage-like THP-1 cells and human primary macrophages. We also addressed the possible involvement of TLR1, TLR2, and CD14 in MMP-9 production in response to LM stimulation.In...

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Differential regulation of MMP-1/9 and TIMP-1 secretion in human monocytic cells in response to Mycobacterium tuberculosis

Cited by 35 publications

References 29 publications

Unopposed Matrix Metalloproteinase-9 Expression in Human Tuberculous Granuloma and the Role of TNF-α-Dependent Monocyte Networks

Unopposed Matrix Metalloproteinase-9 Expression in Human Tuberculous Granuloma and the Role of TNF-α-Dependent Monocyte Networks

Matrix metalloproteinases in tuberculosis

Mycobacterial Lipomannan Induces Matrix Metalloproteinase-9 Expression in Human Macrophagic Cells through a Toll-Like Receptor 1 (TLR1)/TLR2- and CD14-Dependent Mechanism

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