Journal ArticleDOI
Doxycycline and chemically modified tetracyclines inhibit gelatinase A (MMP-2) gene expression in human skin keratinocytes
TLDR
It is concluded that doxycycline and the chemically modified tetracyclines, in addition to inhibiting the MMP activity may also reduce the enzyme expression at the transcriptional level.Abstract:
The mechanism of tetracycline-induced inhibition of matrix metalloproteinases (MMP) was studied by measuring the MMP secretion and MMP-2 mRNA levels in unkeratinizing periodontal ligament epithelial cells and skin keratinocytes cultured in the presence of doxycycline or chemically modified tetracyclines (CMT) lacking antimicrobial activity. Doxycycline, CMT-1, and CMT-8 exerted a direct dose-dependent inhibition of porcine periodontal ligament epithelial cell medium MMP activity as assayed by gelatin enzymography. Both the 92-kDa (MMP-9) and 72-kDa (MMP-2) gelatinases were inhibited by the tetracyclines added to the conditioned medium. Culturing the cells in the presence of the tetracyclines required considerably smaller concentrations to reduce the secreted MMP activity. The drugs were not toxic to the epithelial cells at concentrations from 4 to 250 micrograms/mL up to 24 h of culture. Tetracycline effects on the MMP-2 mRNA levels were studied in human skin keratinocytes using Northern hybridization analysis with a specific cDNA probe. A marked inhibition in the MMP-2 gene expression was observed by 6 h with 5 micrograms/mL of doxycycline, CMT-1 or CMT-8. Doxycycline inhibition was somewhat stronger than the two other tetracyclines. After 24 h of culture with 50 micrograms/mL of the drugs, the total RNA levels also decreased by 33 to 40%. The 72-kDa gelatinase activity in culture medium of the keratinocytes followed roughly the pattern of inhibition of the gene expression. We conclude that doxycycline and the chemically modified tetracyclines, in addition to inhibiting the MMP activity may also reduce the enzyme expression at the transcriptional level.read more
Citations
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Journal ArticleDOI
Matrix metalloproteinases in skin
TL;DR: The role of MMPs and TIMPs in human skin based on new observations on the regulation of the expression of M MPs, on their substrate specificily, and MMP expression in physiologic and pathologic conditions of skin involving matrix remodeling are discussed.
Journal ArticleDOI
A novel mechanism of action of tetracyclines: Effects on nitric oxide synthases
Ashok R. Amin,Mukundan Attur,Geeta D. Thakker,Prakash D. Patel,Pranav Vyas,Rajesh N. Patel,I R Patel,Steven B. Abramson +7 more
TL;DR: The studies indicate that a novel mechanism of action of tetracyclines is to inhibit the expression of NOS, which has been implicated in the pathogenesis of arthritis and other inflammatory diseases.
Journal ArticleDOI
Role of thymic peptides as transmitters between the neuroendocrine and immune systems.
TL;DR: The role of MMPs and their inhibitors in tumour invasion as a basis for prognostic purposes and for targeted therapeutic intervention in cancer is discussed.
Journal ArticleDOI
Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression, MAPK activation in the corneal epithelium in experimental dry eye.
Cintia S. de Paiva,Rosa M. Corrales,Arturo L. Villarreal,William J. Farley,De-Quan Li,Michael E. Stern,Stephen C. Pflugfelder +6 more
TL;DR: Both methylprednisolone and doxycycline reduced expression and activity of MMP-9, decreased levels of inflammatory cytokines transcripts and reduced activation of MAPKs in the corneal epithelium in response to EDE.
Journal ArticleDOI
Doxycycline inhibition of aneurysmal degeneration in an elastase-induced rat model of abdominal aortic aneurysm: Preservation of aortic elastin associated with suppressed production of 92 kD gelatinase
Drazen Petrinec,Shixiong Liao,Dennis R. Holmes,Jeffrey M. Reilly,William C. Parks,Robert W. Thompson +5 more
TL;DR: Treatment with an MMP-inhibiting tetracycline inhibits the development of experimental AAA in vivo, and this inhibition may be due to selective blockade of elastolytic MMP expression in infiltrating inflammatory cells.
References
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TL;DR: Using an improved method of gel electrophoresis, many hitherto unknown proteins have been found in bacteriophage T4 and some of these have been identified with specific gene products.
Journal Article
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Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays
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Journal ArticleDOI
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