Effects of tetracyclines on the production of matrix metalloproteinases and plasminogen activators as well as of their natural inhibitors, tissue inhibitor of metalloproteinases-1 and plasminogen activator inhibitor-1

Sadowski, Thorsten; Steinmeyer, Jürgen

doi:10.1007/s000110050742

Cited by 62 publications

(40 citation statements)

References 41 publications

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“…Tetracyclines dose-dependently inhibited MMP-9, and IC50 values of 40.0, 10.7, and 608.0 µM were achieved for tetracycline, minocycline, and doxycycline, respectively. In previous studies on different MMPs using alternative experimental models, IC50 values ranging from 5 to 500 µM have been generally reported (13,(23)(24)(25)(26). In a study on collagenase extracted from rabbit corneas, the inhibitory effects of tetracyclines on enzyme activity were measured using a chromogen substrate (27).…”

Section: Discussionmentioning

confidence: 99%

Minocycline is More Potent Than Tetracycline and Doxycycline in Inhibiting MMP-9 in Vitro

Modheji

Olapour

Khodayar

et al. 2016

Jundishapur J Nat Pharm Prod

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Background: Tetracyclines are antimicrobial agents that possess anti-inflammatory and matrix metalloproteinase (MMP) inhibitory effects. Tetracycline, doxycycline, and minocycline have shown different potencies in inhibiting various MMPs. MMPs are a conserved family of zinc-dependent endopeptidases, which are involved in various physiologic and pathologic conditions. MMP-9 is among the most important proteases involved in the development of cardiovascular disease, cancer, and inflammatory disease Objectives: Considering the central role of MMP-9 in the above-mentioned diseases and the variable inhibitory potentials of routine tetracyclines, including tetracycline, doxycycline, and minocycline, this study measured the inhibitory effect of these routine tetracycline agents on MMP-9 activity obtained from U-937 cell cultures using the zymography method. Materials and Methods: An MMP-9-rich culture medium of U-937 cells was used as the source of the enzyme. Serial dilutions of 5, 20,

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Section: Discussionmentioning

confidence: 99%

Minocycline is More Potent Than Tetracycline and Doxycycline in Inhibiting MMP-9 in Vitro

Modheji

Olapour

Khodayar

et al. 2016

Jundishapur J Nat Pharm Prod

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“…Conversion of plasminogen to plasmin by PAs in alginate samples and cell lysates was recorded by the hydrolysis of the chromogenic substrate H-D-Val-Leu-Lys-pNA (S-2251, Chromogenix, Mölndal, Sweden), as has been described [21]. No activity could be detected in media samples.…”

Section: Determination Of Pa Activitymentioning

confidence: 99%

Differential effects of nonsteroidal antiinflammatory drugs on the IL-1 altered expression of plasminogen activators and plasminogen activator inhibitor-1 by articular chondrocytes

Sadowski

Steinmeyer

2002

Inflamm. res.

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In conclusion, our studies indicate that NSAIDs preferentially inhibit tPA expression by bovine articular chondrocytes. By increasing the production of PAI-1 at therapeutical concentrations meloxicam could reduce PA activity, whereas the other NSAIDs tested mainly enhanced the release of this inhibitor from the extracellular matrix. In how far this would affect the enzyme-inhibitor balance within cartilage has to be determined in further studies.

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“…Clinically, tetracyclines have been used to treat rheumatoid arthritis and various skin disorders, such as inflammatory acne, rosacea, bullous dermatoses, and neutrophilic dermatoses (12,21). The anti-inflammatory activities of tetracyclines include the modulation of lymphocyte activation and neutrophil chemotaxis (6,30), possibly by inhibiting matrix metalloproteinases (20), phospholipase A 2 (19), nitric oxide synthases (2), and/or caspase 1 (33). The ability of tetracyclines to bind Ca 2ϩ and Mg 2ϩ may account for some of those biological activities via the chelation of those cations and their transport into intracellular compartments (34).…”

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confidence: 99%

Tetracyclines Modulate Protease-Activated Receptor 2-Mediated Proinflammatory Reactions in Epidermal Keratinocytes

Ishikawa

Tsuda

Konishi

et al. 2009

Antimicrob Agents Chemother

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In addition to their antibiotic effects, tetracyclines have anti-inflammatory action that is often beneficial in the control of inflammatory skin disorders. In this study, we examined the effects of tetracycline (TET) and two of its derivatives, doxycycline (DOX) and minocycline (MIN), on the production of interleukin-8 (IL-8) elicited by the activation of protease-activated receptor 2 (PAR2) in normal human epidermal keratinocytes (NHEK). In NHEK, the production of IL-8 stimulated by an agonist peptide of PAR2, SLIGKIV-NH 2 , at 100 M was significantly reduced by TET, DOX, or MIN at 5 and 10 M, concentrations that are noncytotoxic. The tumor necrosis factor alpha (TNF-␣)-induced production of IL-8 was synergistically augmented by SLIGKIV-NH 2 , and that synergistic increase in the production of IL-8 was suppressed by 100 nM PAR2-specific small interfering RNA. It was also suppressed by TET, DOX, or MIN but not by the 14-membered-ring macrolide antibiotics erythromycin, roxithromycin, and clarithromycin, which also have anti-inflammatory activities, at 10 M. These results suggest that tetracyclines attenuate the PAR2-IL-8 axis in keratinocytes and thereby effectively modulate proinflammatory responses in the skin.

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Effects of tetracyclines on the production of matrix metalloproteinases and plasminogen activators as well as of their natural inhibitors, tissue inhibitor of metalloproteinases-1 and plasminogen activator inhibitor-1

Abstract: We conclude that the inhibition of MMPs by tetracyclines occurs mainly via down-regulation of the respective gene expression.

Cited by 62 publications

References 41 publications

Minocycline is More Potent Than Tetracycline and Doxycycline in Inhibiting MMP-9 in Vitro

Minocycline is More Potent Than Tetracycline and Doxycycline in Inhibiting MMP-9 in Vitro

Differential effects of nonsteroidal antiinflammatory drugs on the IL-1 altered expression of plasminogen activators and plasminogen activator inhibitor-1 by articular chondrocytes

Tetracyclines Modulate Protease-Activated Receptor 2-Mediated Proinflammatory Reactions in Epidermal Keratinocytes

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