No abstract available.
Angina, Unstable/*enzymology/*immunology ; Female ; Humans ; Inflammation Mediators/*blood ; Interleukins/*blood ; Male ; Matrix Metalloproteinase 9/*blood ; Myocardial Infarction/*enzymology/*immunology ; Tissue Inhibitor of Metalloproteinase-1/*blood

Increased production of matrix metalloproteinases (MMPs) has been associated with increases in invasive and metastatic potential in many types of human carcinoma. Tissue inhibitors of metalloproteinase (TIMP)-1 inhibits most interstitial collagenases and MMP-9. TIMP-2 binds specifically and noncovalently to the pro-form of MMP-2 and inhibits its enzyme activity. In this study, we examined TIMP-1 and TIMP-2 expressions in relation to clinicopathological variables in colorectal carcinoma with in situ hybridization and immunohistochemistry. TIMP-1 and TIMP-2 expressions were localized overwhelmingly to pericancer stromal cells, while malignant and normal mucosal cells were weak or negative. Strong stromal TIMP-1 immunoreactivity correlated with Dukes' stage (p=0.022), status of lymph node metastasis (p=0.044) and poor survival (p= 0.005). The degree of immunohistochemical staining of TIMP-2 did not correlate with all clinicopathological variables. The correlation between enhanced TIMP-1 expression and advanced stage and poor survival suggest a growth promoting activity of TIMP-1 in colorectal carcinoma.
Adenocarcinoma/pathology ; Adenocarcinoma/mortality ; Adenocarcinoma/enzymology* ; Adult ; Aged ; Aged, 80 and over ; Antibodies ; Collagenases/immunology ; Collagenases/genetics* ; Collagenases/analysis ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/mortality ; Colorectal Neoplasms/enzymology* ; DNA Probes ; Female ; Gelatinase A ; Gelatinase B ; Gelatinases/immunology ; Gelatinases/genetics* ; Gelatinases/analysis ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Human ; In Situ Hybridization ; Male ; Metalloendopeptidases/immunology ; Metalloendopeptidases/genetics* ; Metalloendopeptidases/analysis ; Middle Age ; Predictive Value of Tests ; RNA, Messenger/analysis ; Stromal Cells/pathology ; Stromal Cells/enzymology ; Survival Analysis ; Tissue Inhibitor-of Metalloproteinase-2/immunology ; Tissue Inhibitor-of Metalloproteinase-2/genetics* ; Tissue Inhibitor-of Metalloproteinase-2/analysis ; Tissue-Inhibitor of Metalloproteinase-1/immunology ; Tissue-Inhibitor of Metalloproteinase-1/genetics* ; Tissue-Inhibitor of Metalloproteinase-1/analysis

OBJECTIVETo investigate the expressions of matrix metalloprotein-2 (MMP-2) and tissue inhibitor of metallopeptidase inhibitor-1 (TIMP-1) in the renal allografts of patients with chronic active antibody-mediated rejection (ABMR), and explore their role in the pathogenesis of ABMR.

METHODSImmunohistochemistry and computer-assisted image analysis were used to detect the expression of MMP-2 and TIMP-1 in the renal allografts of 46 patients with interstitial fibrosis and tubular atrophy (IF/TA), with 15 normal renal tissue specimens as the control. The association of MMP-2 and TIMP-1 with the pathological grade of IF/TA in ABMR was analyzed.

RESULTSThe expressions of MMP-2 and TIMP-1 significantly increased in the renal tissues of the patients as compared with the normal renal tissues (P<0.05). MMP-2 expression tended to decrease, while TIMP-1 and serum creatinine increased with the pathological grades of IF/TA (P<0.05). In IF/TA group, the expression of TIMP-1 was positively correlated to serum creatinine level (r=0.718, P=0.00<0.05).

CONCLUSIONAbnormal expressions of MMP-2 and TIMP-1 can promote the development of renal fibrosis in chronic ABMR.

Adult ; Antibody Formation ; Complement C4b ; metabolism ; Female ; Fibrosis ; etiology ; Graft Rejection ; immunology ; Humans ; Kidney ; metabolism ; Kidney Diseases ; pathology ; Kidney Transplantation ; adverse effects ; immunology ; Male ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Middle Aged ; Peptide Fragments ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism

OBJECTIVETo study the influence of hepatocyte growth factor (HGF) antibody on the lung expression level of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1).

METHODSThirty male Wistar rats were randomly divided into 3 groups: control group, model group, and intervention group. Endotoxin was intratracheally infused in the model and intervention groups. HGF antibody was injected in the rats of the intervention group from day 1 to day 14, while the same volume of saline was injected in the control group. The rats were sacrificed on day 28 after endotoxin treatment. The amounts of MMP-9 mRNA and TIMP-1 mRNA were measured by reverse transcription-polymerase chain reaction, and protein expression levels of MMP-9 and TIMP-1 were measured by immunohistochemistry.

RESULTSIn the model group, both mRNA and protein expression levels of TIMP-1 were significantly increased, the same as MMP-9. In the intervention group, the increase of TIMP-1 was remarkably reduced compared with the model group, while the mRNA and protein expression levels of MMP-9 were still increased.

CONCLUSIONHGF activity may accelerate the repair of lung injury through contrary regulating the expression levels of TIMP-1 and MMP-9.

Acute Lung Injury ; metabolism ; pathology ; Animals ; Antibodies ; immunology ; Hepatocyte Growth Factor ; physiology ; Male ; Matrix Metalloproteinase 9 ; analysis ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-1 ; analysis ; genetics

This study is to investigate the tumor invasion and metastasis inhibition effects of the immunoconjugate composed of lidamycin and anti-type IV collagenase monoclonal antibody Fab' fragment. Boyden chamber assay was used to evaluate the influence of Fab'-LDM on HT-1080 cells invasion ability, gelatinase spectrum was used to measure the change of invasion factor MMP-2 and MMP-9's secretion, and RT-PCR was adopted to determine TIMP-1 mRNA expression level. The immunoconjugate inhibition of tumor in situ metastasis was also tested in nude mice. The Fab'-LDM conjugates had dose-dependent inhibition effect on HT-1080 cells' invasion. At the concentrations of 5 and 10 nmol L(-1), the Fab'-LDM inhibited the invasion by (60 +/- 12) % and (79 +/- 11) % respectively. At the concentration of 5 and 10 nmol L(-1), the Fab'-LDM inhibited the secretion of MMP-2 by (42 +/- 8) % and (54 +/- 6) % and that of MMP-9 by (57 +/- 3) % and (87 +/- 1) %, respectively. RT-PCR indicated that conjugates increased the anti-invasion factor TIMP-1 level. The in vivo experiment showed that, compared with the control group, the tumor inhibition rate in Fab', Fab'-LDM, and LDM group equaled to (30 +/- 13) %, (86 +/- 26) %, (74 +/- 22) % respectively. In conclusion, Fab'-LDM could inhibit the invasion and metastasis of tumor and it might be a new tumor biotherapy agent.
Aminoglycosides ; pharmacology ; Animals ; Antibiotics, Antineoplastic ; pharmacology ; Antibodies, Monoclonal ; immunology ; Cell Line, Tumor ; Enediynes ; pharmacology ; Fibrosarcoma ; metabolism ; pathology ; Humans ; Immunoconjugates ; pharmacology ; Immunoglobulin Fab Fragments ; pharmacology ; Matrix Metalloproteinase 2 ; immunology ; secretion ; Matrix Metalloproteinase 9 ; immunology ; secretion ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Transplantation ; RNA, Messenger ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Tumor Burden ; drug effects

Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg·kg. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; Blood-Brain Barrier ; drug effects ; enzymology ; immunology ; Brain ; Brain Ischemia ; drug therapy ; enzymology ; genetics ; Caffeic Acids ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Lactates ; administration & dosage ; Male ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology ; genetics ; immunology ; prevention & control ; Salvia miltiorrhiza ; chemistry ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Transcription Factor RelA ; genetics ; immunology

BACKGROUND/AIMS: Acute coronary syndrome (ACS) is characterized by increased inflammatory processes and endothelial activation. We investigated the association between ACS and inflammatory mediators and matrix-degrading enzymes. METHODS: We prospectively enrolled 55 consecutive patients with ACS: 25 with unstable angina (UA) and 30 with non-ST elevated myocardial infarction (NSTEMI). For comparison, 25 age- and sex-matched subjects with no significant coronary artery stenosis were included as the control group. Peripheral serum levels of interleukin (IL)-33, matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP-1, and C-reactive protein (CRP) were measured on admission, and at 12, 24, 48, and 72 hours after the initial evaluation. RESULTS: Compared to serum levels in the control group, serum levels of IL-33 decreased in the NSTEMI group (p < 0.05), and levels of MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 increased in the UA group (p < 0.01, p < 0.05, respectively) and NSTEMI group (p < 0.05, p < 0.05, respectively). IL-33 levels were significantly lower on admission than at 12 hours after the initial evaluation (p < 0.05). IL-33 levels were negatively correlated with MMP-9 levels (r = -0.461, p < 0.05) and CRP levels (r = -0.441, p < 0.05). CONCLUSIONS: Elevated levels of MMP-9, TIMP-1, and decreased levels of IL-33 play a role in the development and progression of ACS.
Adult ; Angina, Unstable/blood/*enzymology/*immunology ; Biological Markers/blood ; C-Reactive Protein/metabolism ; Case-Control Studies ; Disease Progression ; Female ; Humans ; Inflammation Mediators/*blood ; Interleukins/*blood ; Male ; Matrix Metalloproteinase 9/*blood ; Middle Aged ; Myocardial Infarction/blood/*enzymology/*immunology ; Time Factors ; Tissue Inhibitor of Metalloproteinase-1/*blood

BACKGROUND: Ischemic stroke is a complex condition influenced by many factors. Previous studies have demonstrated that inflammatory markers might play a role in such vascular diseases. Therefore the purpose of this study was to compare the expression of inflammatory markers in Korean ischemic stroke patients and to investigate their relationship to APOE polymorphism. METHODS: The patient group consisted of 275 patients with large artery atherosclerosis (LAA, n=169) and small artery occlusion (SAO, n=106). One hundred and nineteen age matched healthy subjects were recruited as the control group. Serum levels of three inflammatory markers (matrix metalloproteinase, MMP-9; tissue inhibitor of metalloproteinase-1, TIMP-1; and high-sensitivity C-reactive protein, hs-CRP) were measured in each patient by using commercially available kits. Comparison of clinical risk factors, inflammatory marker levels, and APOE genotypes between the stroke patient group and control group and between the two patient subgroups was assessed. RESULTS: Comparison of the stroke group to control group showed significantly elevated levels of circulating MMP-9 (P<0.01) and hs-CRP (P=0.01). Comparison between the individual subgroups revealed a significantly higher level of only TIMP-1 in the LAA subgroup compared to the SAO subgroup (P<0.01). There was no significant difference in inflammatory marker levels among each allele carrier. CONCLUSIONS: The present study revealed the obvious tendency of increased circulating inflammatory markers in the patients with acute ischemic attack, especially MMP-9 and hs-CRP. Our observations suggest that measurement of serum MMP-9, TIMP-1, and hs-CRP levels may be useful in the diagnosis of ischemic stroke patients.
Aged ; Apolipoproteins E/*genetics ; Biological Markers/blood ; Brain Ischemia/complications/*diagnosis ; C-Reactive Protein/analysis ; Carotid Artery Diseases/complications ; Female ; Genotype ; Humans ; Inflammation Mediators/*blood ; Korea ; Male ; Matrix Metalloproteinase 9/blood ; Middle Aged ; Polymorphism, Genetic ; Stroke/*diagnosis/etiology/immunology ; Tissue Inhibitor of Metalloproteinase-1/blood