Neutral metalloproteinases produced by human mononuclear phagocytes. Enzyme profile, regulation, and expression during cellular development.

Welgus, Howard G.; Campbell, Edward J.; Cury, James; Eisen, Arthur Z.; Senior, Robert M.; Wilhelm, Scott M.; Goldberg, Gregory I.

doi:10.1172/jci114867

Cited by 418 publications

(226 citation statements)

References 42 publications

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“…This activity of activin A in the macrophages partly overlaps but is clearly distinct from that of TGF-␤; TGF-␤ stimulated both MMP-2 and MMP-9 production, but blocked LPS-induced MMP-9 expression in mouse peritoneal macrophages (46). Considering that MMP-2 constitutes rate-limiting proteinase governing the degradation of basement membrane collagens (47), activin A might be involved in the migration and infiltration of macrophages through the basement membrane in an inflammatory state, which would be a different role from that of TGF-␤, a well-known anti-inflammatory cytokine (48 -52).…”

Section: Discussionmentioning

confidence: 99%

Activin A Stimulates Type IV Collagenase (Matrix Metalloproteinase-2) Production in Mouse Peritoneal Macrophages

Ogawa

Funaba

Mathews

et al. 2000

The Journal of Immunology

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The role of activin, a dimer of inhibin β subunit, in mouse peritoneal macrophages was evaluated. Activin activity in the cultured macrophages was augmented in response to activation by LPS. In Western blot analysis, immunoreactive activin A was detected in the culture medium only when the macrophages were stimulated by LPS. Although mRNA expression of βA subunit was detected, that of α and βB subunit was not found in macrophages by reverse RT-PCR. The activin βA mRNA level was increased in macrophages by LPS, suggesting that the activin production augmented by LPS is regulated at the mRNA level of the βA gene. The mRNAs of four activin receptors (ActRI, ActRIB, ActRII, and ActRIIB) were also detected in the peritoneal macrophages, and the mRNA levels, except for ActRIB, were decreased during the LPS treatment. Exogenous activin A stimulated the mRNA expression and gelatinolytic activity of matrix metalloproteinase-2 (MMP-2) in macrophages in both the presence and the absence of LPS. In contrast, activin did not affect the production of MMP-9 in macrophages. These results suggested that 1) mouse peritoneal macrophages produced activin A; 2) expression of activin A was enhanced with activation of the macrophages; 3) the macrophages also expressed activin receptors; and 4) exogenous activin A stimulated MMP-2 expression and activity, implicating activin A as an positive regulator of MMP-2 expression. Considering that MMP-2 constitutes the rate-limiting proteinase governing the degradation of basement membrane collagens, activin A may be involved in migration and infiltration of macrophages through the basement membrane in an inflammatory state.

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Section: Discussionmentioning

confidence: 99%

Activin A Stimulates Type IV Collagenase (Matrix Metalloproteinase-2) Production in Mouse Peritoneal Macrophages

Ogawa

Funaba

Mathews

et al. 2000

The Journal of Immunology

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“…As many tumours produce factors such as macrophage colony-stimulating factor (M-CSF) (Walter et al 1991) and as TAM may bear receptors for M-CSF (Bottazi et al 1990), tumour cells may stimulate the migration and growth of tumour-associated macrophages to the tumour edge, leading to increased local MMP-9 production facilitating tumour invasion. This notion is supported by the identification of agents such as lipopolysaccharide (LPS), which can stimulate macrophages to produce several MMPs including MMP-9 (Welgus et al 1990;Xie et al 1994). as well as our work, which demonstrates that metastastic CRC cells can stimulate THP-1 monocytes to produce MMP-9 (Swallow et al 1996).…”

Section: Discussionmentioning

confidence: 99%

Unique activation of matrix metalloproteinase-9 within human liver metastasis from colorectal cancer

Zeng

Guillem²

1998

Br J Cancer

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Summary Expermental in vitro and animal data support an important role for matrix metalloproteinases (MMPs) in cancer invasion and metastasis via proteolytic degradation of the extracellular matrix (ECM). Our previous data have shown that MMP-9 mRNA is localized to the interface between liver metastasis and normal liver tissue, indicating that MMP-9 may play an important role in liver metastasis formation. In the present study, we analysed the cellular enzymatic expression of MMP-9 in 18 human colorectal cancer (CRC) liver metastasis specimens by enzyme-linked immunosorbent assay (ELISA) and zymography. ELISA anatysis reveals that the latent form of MMP-9 is present in both liver metastasis and paired adjacent normal liver tissue. The mean level of the latent form of MMP-9 is 580±270 ng per mg total tissue protein (mean ± s.e.) in liver metastasis vs 220 ± 90 in normal liver tissue. However, this difference is not significantly different (P = 0.26). Using gelatin zymography, the 92-kDa band representative of the latent form is present in both liver metastasis and normal liver tissue. However, the 82 kDa band, representive of the active form of MMP-9, was seen only in liver metastasis. This was confirmed by Westem blot analysis. Our observation of the unique presence of the active form of MMP-9 within liver metastasis suggests that proMMP-9 activation may be a pivotal event during CRC liver metastasis formation. . emphasizing the clinical importance of elevated MMP-9 expression in primarx CRC.We hax-e previously demonstrated that MMP-9 mRRNA is localized in the interface between lixer metastasis and normal lixer tissue. indicating that MMP-9 may play an important role in lix er metastasis formation. To inxestigate further the significance of elexated MMP-9 RNA in liver metastasis formation. the present study examined MMP-9 enzy matic expression in CRC liver metastasis. MATERIALS AND METHODS

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“…Matrix metalloproteinases (MMPs) are structurally related, zinc-containing enzymes that degrade extracellular matrix (4,5). Matrix metalloproteinase-9 (MMP-9 or 92-kDa gelatinase-B) is quantitatively the most important of several MMPs secreted by monocytes and macrophages and is pivotal in this response (6,7). MMP-9 specifically degrades type IV and V collagens present in the basement membrane associated with CNS endothelial cells and is thought to facilitate leukocyte migration across the blood-brain barrier (8 -10).…”

Section: Identification Of a Matrix-degrading Phenotype In Humanmentioning

confidence: 99%

Identification of a Matrix-Degrading Phenotype in Human Tuberculosis In Vitro and In Vivo

Price

Farrar

Tran

et al. 2001

The Journal of Immunology

101

116

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Tuberculous meningitis is characterized by cerebral tissue destruction. Monocytes, pivotal in immune responses to Mycobacterium tuberculosis, secrete matrix metalloproteinase-9 (MMP-9), which facilitates leukocyte migration across the blood-brain barrier, but may cause cerebral injury. In vitro, human monocytic (THP-1) cells infected by live, virulent M. tuberculosis secreted MMP-9 in a dose-dependent manner. At 24 h, MMP-9 concentrations increased 10-fold to 239 ± 75 ng/ml (p = 0.001 vs controls). MMP-9 mRNA became detectable at 24–48 h. In contrast, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) gene expression and secretion were similar to constitutive levels from controls at 24 h and increased just 5-fold by 48 h. In vivo investigation revealed MMP-9 concentration per leukocyte in cerebrospinal fluid (CSF) from tuberculous meningitis patients (n = 23; median (range), 3.19 (0.19–31.00) ng/ml/cell) to be higher than that in bacterial (n = 12; 0.23 (0.01–18.37) ng/ml/cell) or viral meningitis (n = 20; 0.20 (0.04–31.00) ng/ml/cell; p < 0.01). TIMP-1, which was constitutively secreted into CSF, was not elevated in tuberculous compared with bacterial meningitis or controls. Thus, a phenotype in which MMP-9 activity is relatively unrestricted by TIMP-1 developed both in vitro and in vivo. This is functionally significant, since MMP-9 concentrations per CSF leukocyte (but not TIMP-1 concentrations) were elevated in fatal tuberculous meningitis and in patients with signs of cerebral tissue damage (unconsciousness, confusion, or neurological deficit; p < 0.05). However, MMP-9 activity was unrelated to the severity of systemic illness. In summary, M. tuberculosis-infected monocytic cells develop a matrix-degrading phenotype, which was observed in vivo and relates to clinical signs reflecting cerebral injury in tuberculous meningitis.

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Neutral metalloproteinases produced by human mononuclear phagocytes. Enzyme profile, regulation, and expression during cellular development.

Cited by 418 publications

References 42 publications

Activin A Stimulates Type IV Collagenase (Matrix Metalloproteinase-2) Production in Mouse Peritoneal Macrophages

Activin A Stimulates Type IV Collagenase (Matrix Metalloproteinase-2) Production in Mouse Peritoneal Macrophages

Unique activation of matrix metalloproteinase-9 within human liver metastasis from colorectal cancer

Identification of a Matrix-Degrading Phenotype in Human Tuberculosis In Vitro and In Vivo

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