Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We explored whether the serum concentration of interleukin 6 (IL-6) is associated with matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in rheumatoid arthritis (RA) patients. Serum levels of IL-6, interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1 and TIMP-2 were assessed with an ELISA technique in 30 RA patients. We observed the association between IL-6 and MMP-1 (p < 0.001), MMP-3 (p < 0.05), MMP-9 (p < 0.001), TIMP-1 (p < 0.01) and TIMP-2 (p < 0.05). Additionally, serum IL-6, measured MMPs and TIMP-1 correlated with the erythrocyte sedimentation rate, C reactive protein plasma level and the number of swollen joints. We suggest that assessing the serum IL-6, MMP-1, MMP-3, MMP-9 and TIMP-1 levels may be helpful in the prediction of the RA activity.
Pol Arch Med Wewn 2003 Feb
PMID:[Serum interleukin 6 (il-6A) concentration correlates with matrix metalloproteinases and their tissue inhibitors in rheumatoid arthritis]. 1287 74

Tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinases (MMPs) play an important role in the pathogenesis of rheumatoid arthritis (RA). The present study was conducted to investigate whether the serum level of TNF-alpha is correlated with MMPs and tissue inhibitors of metalloproteinases (TIMPs) in RA patients. Serum concentrations of TNF-alpha, interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1 and TIMP-2 were measured by ELISA in 34 patients with RA. We found the TNF-alpha to correlate with MMP-1, MMP-3, MMP-9 and total measured MMPs serum concentrations (p < 0.05 for all comparisons). Furthermore, serum TNF-alpha, MMP-1 MMP-3, MMP-9 and TIMP-1 levels correlated with markers of disease activity such as the erythrocyte sedimentation rate, C reactive protein level and the number of swollen joints. No associations were observed between TNF-alpha and TIMPs serum concentrations. Our results support the concept of the regulation of the MMPs synthesis by cytokines such as TNF-alpha. We conclude that the measurement of the serum TNF-alpha, MMPs and TIMP-1 concentrations may be useful in the assessment of RA activity.
Pol Merkur Lekarski 2003 May
PMID:[Correlation between tumor necrosis factor alpha and matrix metalloproteinases levels in serum of patients with rheumatic arthritis]. 1293 14

Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading extracellular matrix. Their role has been emphasized in tumor invasion, metastasis and tumor-induced angiogenesis. The gene encoding MMP-3 is polymorphic and an insertion (6A)/deletion (5A) polymorphism (5A/6A polymorphism) in the MMP-3 gene may have functional significance in the regulation of its expression. In the present work the distribution of genotypes and frequency of alleles of the 5A/6A polymorphism in subjects with ovarian cancer were investigated. Paraffin embedded tumor tissues were obtained from 118 postmenopausal women with node-negative and node-positive ovarian cancer. The 5A/6A polymorphism was determined by PCR amplification using the allele specific primers. The distribution of the genotypes of the 5A/6A polymorphism in both control and study patients did not differ significantly (p>0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p>0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. The results suggest that the 5A/6A polymorphism of MMP-3 gene may not be linked with appearance and/or progression of ovarian cancer.
Pol J Pathol 2003
PMID:PCR analysis of matrix metalloproteinase 3 (MMP-3) gene promoter polymorphism in ovarian cancer. 1499 90

The most dangerous environmental factor for our skin condition is ultraviolet light radiation. Chronic exposition to ultraviolet light can induce epidermal atrophy, keratosis, depigmentation and dysplasia. In the dermis, UV light causes dramatic up-regulation of extracellular matrix-degrading enzymes. Matrix metalloproteinases (MMPs) are engaged in collagen, elastin and other extracellular matrix components degradation. In addition, to increase level of destructive enzymes, UV light has been shown to decrease collagen production. As a consequence of UV impact on skin, it shows signs of aging including loss of tone and elasticity, increased skin fragility, blood vessels weakness and wrinkles. The most dangerous effect of UV on skin is an increased risk of melanoma and other skin cancers. Retinoids are well known antiaging agents. For many years this vitamin has been used for the prevention and treatment of photoaging. Retinoids abolish cellular atypia, increase compacting of the stratum corneum and reduce skin hyperpigmentation caused by sun light. Recent evidence suggests that retinoids also play a role in the prevention of aging, because of its inhibitory effects on metalloproteinases expression. The aim of this study was to examine if all-trans-retinoic acid (ATRA) effects MMP-1, MMP-2, MMP-3 and MMP-14 gene expression in fibroblasts cultured in vitro.
Acta Pol Pharm
PMID:Influence of retinoids on skin fibroblasts metabolism in vitro. 1853 79

Inositol hexaphosphate (IP6) is a naturally occurring phytochemical, found in abundance in cereals, legumes and other high-fiber-content diets. IP6 has shown promising efficacy against a wide range of cancers. Its anti-cancer activity involves anti-proliferative, pro-apoptotic and anti-metastatic effects. Both matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), are implicated in tumor growth, metastasis, and angiogenesis. Phorbol-12-myristate 13-acetate (PMA) is a well-known inflammatory stimulator and tumor promoter that activates PKC and increases the invasiveness of various types of cancer cells by activating MMPs. The aim of the present study was to examine the influence of IP6 on the expression of selected MMPs, i.e., MMP-1, -2, -3, -9, 10, -13 and their TIMP-1 and -2 in unstimulated and PMA-stimulated colon cancer cell line Caco-2. Quantification of genes expression in Caco-2 cells treated with 100 ng/mL of PMA, 2.5 mM of IP6 and both for 6 and 12 h was carried out using real time QRT-PCR technique. Stimulation of cells with PMA resulted in an up-expression of MMP-2, MMP-3, MMP-9, MMP-10, MMP-13 and TIMP-1 mRNAs and decrease in MMP-1 gene expression. The quantity of TIMP-2 transcript was reduced by PMA. A significant decrease in MMP-2, MMP-3, MMP-10, MMP-13, and TIMP-1 expression in response to IP6 was observed. IP6 down-regulated MMP-9 transcription induced by PMA and decreased the level of both MMP-2 and MMP-3 mRNAs in PMA-stimulated cells. Caco-2 treated with both PMA and IP6 showed a significant decrease in MMP-1 expression in comparison to PMA-stimulated cells. The results of this study show that PMA can modulate MMP and TIMP genes transcription in colon cancer cells Caco-2. IP6 exerts an influence of basal mRNA expression of some MMPs and their tissue inhibitors and down-regulates MMP-1, MMP-2, MMP-3 and MMP-9 in cells treated with PMA. IP6 could be an effective anti-metastatic agent that suppresses expression of MMP genes at transcription level.
Acta Pol Pharm
PMID:Inhibitory effect of inositol hexaphosphate on metalloproteinases transcription in colon cancer cells stimulated with phorbol-12-myristate 13-acetate. 2328 95

In pulmonary tuberculosis (TB), the inflammatory immune response against Mycobacterium tuberculosis (Mtb) is associated with tissue destruction and cavitation, which drives disease transmission, chronic lung disease, and mortality. Matrix metalloproteinase (MMP)-1 is a host enzyme critical for the development of cavitation. MMP expression has been shown to be epigenetically regulated in other inflammatory diseases, but the importance of such mechanisms in Mtb-associated induction of MMP-1 is unknown. We investigated the role of changes in histone acetylation in Mtb-induced MMP expression using inhibitors of histone deacetylases (HDACs) and histone acetyltransferases (HAT), HDAC siRNA, promoter-reporter constructs, and chromatin immunoprecipitation assays. Mtb infection decreased Class I HDAC gene expression by over 50% in primary human monocyte-derived macrophages but not in normal human bronchial epithelial cells (NHBEs). Non-selective inhibition of HDAC activity decreased MMP-1/-3 expression by Mtb-stimulated macrophages and NHBEs, while class I HDAC inhibition increased MMP-1 secretion by Mtb-stimulated NHBEs. MMP-3 expression, but not MMP-1, was downregulated by siRNA silencing of HDAC1. Inhibition of HAT activity also significantly decreased MMP-1/-3 secretion by Mtb-infected macrophages. The MMP-1 promoter region between -2,001 and -2,942 base pairs from the transcriptional start site was key in control of Mtb-driven MMP-1 gene expression. Histone H3 and H4 acetylation and RNA Pol II binding in the MMP-1 promoter region were increased in stimulated NHBEs. In summary, epigenetic modification of histone acetylation via HDAC and HAT activity has a key regulatory role in Mtb-dependent gene expression and secretion of MMP-1 and -3, enzymes which drive human immunopathology. Manipulation of epigenetic regulatory mechanisms may have potential as a host-directed therapy to improve outcomes in the era of rising TB drug resistance.
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PMID:Epigenetic Regulation of Matrix Metalloproteinase-1 and -3 Expression in Mycobacterium tuberculosis Infection. 2859 72