We-P14:422 Olive oil phenols modulate TNF-alpha-induced matrix metalloproteinase-9 in THP-1 cells

Epidemiology and pathogenesis of cardiovascular diseases (CVD) and osteoporosis are strikingly overlapping. This study presents matrix metalloproteinase-9 (MMP-9), as a simple molecular link more consistently associated with the pathophysiology of both osteoporosis and CVD risk factors. 40 adult female rats were randomly distributed into 4 groups [control sham-operated, untreated osteoporosis, carvedilol-treated osteoporosis and alendronate-treated osteoporosis]. After 8 weeks, blood samples were collected to estimate Lipid profile (Total cholesterol, HDL, Triglycerides), inflammatory markers (IL-6, TNF alpha, CRP and NO), and Bone turnover markers (BTM) (Alkaline phosphatase, osteocalcin and pyridinoline). The tibias were dissected to estimate MMP-9 and NF-kB gene expression, OPG, RANKL levels and for histological examination. Induction of osteoporosis resulted in a significant elevation in BTM, inflammatory markers and dyslipidemia. MMP-9 was significantly elevated and positively correlated with BTM, inflammation and dyslipidemia markers. Carvedilol and alendronate exerted a bone preservative role and attenuated dyslipidaemia and inflammation in accordance with their respective effect on MMP-9.

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Anetoderma with lesional infiltration of TNF-alpha-expressing basophils and matrix metalloproteinase-9-secreting M2 macrophages

European Journal of Dermatology ◽

10.1684/ejd.2021.3998 ◽

2021 ◽

Vol 31 (2) ◽

pp. 258-259

Author(s):

Takashi Hashimoto ◽

Kayo Awatani ◽

Takahiro Satoh

Keyword(s):

Matrix Metalloproteinase ◽

Matrix Metalloproteinase 9 ◽

Tnf Alpha ◽

M2 Macrophages ◽

Metalloproteinase 9

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CGP-42112 partially activates human monocytes and reduces their stimulation by lipopolysaccharides

AJP Cell Physiology ◽

10.1152/ajpcell.1997.273.3.c826 ◽

1997 ◽

Vol 273 (3) ◽

pp. C826-C833 ◽

Cited By ~ 14

Author(s):

G. Egidy ◽

J. Friedman ◽

M. Viswanathan ◽

L. M. Wahl ◽

J. M. Saavedra

Keyword(s):

Angiotensin Ii ◽

Matrix Metalloproteinase ◽

Transforming Growth Factor ◽

Matrix Metalloproteinase 9 ◽

Tnf Alpha ◽

Dependent Manner ◽

Human Monocytes ◽

Binding Studies ◽

Metalloproteinase 9 ◽

At2 Receptors

CGP 42112, a high-affinity ligand for angiotensin II AT2 receptors, binds to rat macrophage/microglia lacking AT2 receptors. Here we report that CGP-42112 binds to human monocytes and exerts specific effects. Binding studies revealed a single site, highly specific for CGP-42112, not displaceable by angiotensin II, angiotensin fragments, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4, IL-10, transforming growth factor-beta, or lipopolysaccharide (LPS). Incubation of purified human monocytes in serum-free medium with CGP-42112 enhanced, in a dose-dependent manner, cell attachment to fibronectin and collagen-coated dishes as well as matrix metalloproteinase-9 secretion. CGP-42112 did not promote cytokine secretion. In contrast, when added in the presence of low doses of LPS, CGP-42112 reduced the LPS-stimulated secretion of TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6 without affecting IL-10 and decreased the LPS-stimulated matrix metalloproteinase-9 activity. Additionally, CGP-42112 inhibited the increase in protein kinase A activity produced by LPS. Our results indicate that CGP-42112 may modulate monocyte activation through binding to a novel receptor.

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Matrix metalloproteinase-9 (92 kDa gelatinase/type IV collagenase) from U937 monoblastoid cells: correlation with cellular invasion

Journal of Cell Science ◽

10.1242/jcs.104.4.991 ◽

1993 ◽

Vol 104 (4) ◽

pp. 991-999 ◽

Cited By ~ 13

Author(s):

H. Watanabe ◽

I. Nakanishi ◽

K. Yamashita ◽

T. Hayakawa ◽

Y. Okada

Keyword(s):

Matrix Metalloproteinase ◽

Matrix Metalloproteinase 9 ◽

Mononuclear Phagocytes ◽

Cathepsin G ◽

Tnf Alpha ◽

U937 Cells ◽

Type Iv Collagenase ◽

Leukocyte Elastase ◽

Type Iv ◽

Metalloproteinase 9

The role of matrix metalloproteinase-9 (MMP-9, 92 kDa gelatinase/type IV collagenase) in invasion of mononuclear phagocytes was studied with U937 monoblastoid cells. 12-o-tetradecanoyl 13-phorbol acetate (TPA) differentiated them to macrophage-like cells with induction of MMP-9, and tumor necrosis factor alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) stimulated the production of MMP-9 by TPA-treated cells. TNF alpha also induced the production of MMP-9 by TPA-untreated U937 cells without morphological differentiation. Other agents including dimethyl sulfoxide (DMSO), all-trans-retinoic acid (all-trans-RA), platelet-derived growth factor and 3′;5′-cyclic monophosphate had no effects on MMP-9 production by TPA-treated or -untreated cells, but all-trans-RA and DMSO did have a morphological effect on the differentiation of the cells. These data suggest that MMP-9 production by U937 cells is regulated by a mechanism independent of the differentiation to macrophage-like cells. MMP-9 was purified to homogeneity as an inactive zymogen with M(r) 92,000 (proMMP-9) from TPA-differentiated U937 cells treated with TNF alpha. ProMMP-9 was activated by p-aminophenylmercuric acetate (APMA) generating an active species of M(r) 67,000. Trypsin and cathepsin G also attained activation of the zymogen to its full activity obtained by APMA activation, but plasmin, leukocyte elastase, thrombin and plasma kallikrein had no ability to activate it. APMA-activated MMP-9 degraded type I gelatin readily and cleaved native collagen types III, IV and V. Invasion assays using reconstituted basement membrane coupled with a type IV collagenolysis assay showed good correlations between invasiveness, type IV collagenolysis and proMMP-9 production. Invasion was significantly inhibited by EDTA, alpha 2-macroglobulin and tissue inhibitor of metalloproteinases-1, but not by inhibitors of cathepsin G and leukocyte elastase. These data suggest that MMP-9 plays an important role in the invasion of mononuclear phagocytes through basement membranes.

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