Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In murine schistosomiasis mansoni, eggs deposited in the liver and intestines induce a cell-mediated granulomatous reaction. Previous studies have shown that maximal granuloma size differs in the liver and various segments of the gastrointestinal tract. The objective of this investigation was to isolate intestinal granulomas and to determine whether organ-dependent differences in cell composition and granuloma function exist. Intestinal granulomas representative of those in tissue were isolated by a combination of chemical and mechanical techniques. When dissociated by collagenase, these lesions yielded a viable heterogeneous population of inflammatory cells. Granulomas from the liver, colon, and ileum showed differences in cellular composition. Liver lesions contained the largest number of T and B lymphocytes, eosinophils, and mast cells whereas ileal granulomas comprised mostly macrophages. Immunofluorescence studies on frozen tissue sections revealed that T and B lymphocytes also displayed different patterns of distribution within granulomas from different tissues. In contrast to isolated cultured liver granulomas that produced MIF-like substances, isolated colonic and ileal granulomas had weak or no MIF activity. It thus appears that granuloma formation in various organs is influenced by local factors that could affect the ultimate resolution of the lesions.
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PMID:Organ-dependent differences in composition and function observed in hepatic and intestinal granulomas isolated from mice with Schistosomiasis mansoni. 660 Jan 90

There is a dearth of knowledge on the tissue fibrosis that contributes to the pathology of schistosomiasis mansoni. The present study was designed to test the direct effect of live schistosome eggs and soluble egg antigens (SEA) on cultured normal human fibroblasts. Coincubation for 3 days of fibroblast monolayers with 100-500 live eggs/ml medium or equivalent amounts of SEA caused enhanced incorporation of labelled proline. The newly synthesized polypeptides were sensitive to purified collagenase enzyme activity. Collagen synthesis was also verified by measuring increased hydroxyproline content in fibroblasts. Whereas low numbers of eggs stimulated fibroblast activity, 500 eggs/ml medium caused a disarray in the arrangement of cells, with cytoplasmic granulation, cell detachment and death. These results indicate that fibroblast stimulation and collagen synthesis may also be triggered by the direct action of egg secretions on tissue fibroblasts.
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PMID:Induction of collagen synthesis in cultured human fibroblasts by live Schistosoma mansoni eggs and soluble egg antigens (SEA). 668 91

This work was designed to assess the reflection of early treatment by praziquantel (CAS 55268-74-1, EMBAY 8440, Biltricide) on serum connective tissue metabolite markers (hyaluronic acid and procollagen III peptide) in patients with active intestinal schistosomiasis. Children and adolescent subjects from primary and secondary schools in an endemic area of schistosomiasis mansoni were included. Age-matched subjects from an urban area served as normal controls. All subjects were examined clinically and parasitologically. Detection of hepatitis B seromarkers was also done. The infected subjects were treated with praziquantel at a dose of 60 mg/kg of body weight which was repeated after 4 weeks. Serum hyaluronic acid and procollagen III peptide were measured by radioimmunoassay. High hyaluronic acid was encountered in infected subjects when compared to their respective age-matched controls. Significant decrease of 4 and 8 weeks post-treatment was noted when compared to ist level before treatment. There was no significant change in serum procollagen III peptide on comparing infected subjects to their controls, whereas a significant increase was observed in its level after 4 and 8 weeks post-treatment compared to that before treatment. This work suggests that early treatment of intestinal schistosomiasis with specific chemotherapy (praziquantel) decreases serum hyaluronic acid and increases procollagen III peptide probably via downregulation of granulomatous inflammatory cell reaction and activation of collagenase enzymes, respectively.
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PMID:Effect of early treatment with praziquantel on serum connective tissue metabolite markers in children and adolescents with intestinal schistosomiasis mansoni. 903 50

In schistosomiasis mansoni, granulomatous inflammation and fibrotic resolution are the major pathogenetic factors. The outcome of fibrosis is influenced by the deposition of collagen and degradation mediated by matrix metalloproteinases (MMP). There is a dearth of data on the expression of MMP and the tissue inhibitors of metalloproteinase (TIMP) during the fibrosis associated with schistosomiasis. In this study, the dynamics of collagen, MMP and TIMP gene expression were analysed during murine Schistosoma mansoni infection. Expression within the granulomatous liver tissue of the genes coding for collagen of types I, III and IV was up-regulated at the onset of granuloma development, and the dominant type-I expression peaked at the chronic, fibrotic stage. The amount of deposited hepatic collagen increased with the chronicity of the infection, indicating cumulative fibrosis. Collagenase, gelatinase, stromelysin, matrilysin-specific gene activities were similarly up-regulated, but only MMP-8 (collagenase-2) expression peaked at the height of fibrosis. TIMP-1 gene expression gradually increased during the course of the disease and, along with TIMP-2, peaked at the chronic, fibrotic stage. Granuloma myofibroblasts expressed both MMP and TIMP-1 genes. In ELISA of the splenic cytokines, high levels of fibrogenic interleukin-13 and moderate production of transforming growth factor-beta were found to be concurrent with fibrosis. These data indicate that an imbalance in MMP:TIMP expression and fibrogenic cytokine production are associated with cumulative fibrosis.
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PMID:Dynamics of collagen, MMP and TIMP gene expression during the granulomatous, fibrotic process induced by Schistosoma mansoni eggs. 1532 65

Schistosomiasis mansoni disseminated worm eggs in mice and humans induce granulomatous inflammations and cumulative fibrosis causing morbidity and possibly mortality. In this study, intrahepatic and I.V. injections of a double-stranded oligodeoxynucleotide decoy containing the TGF-beta regulatory element found in the distal promoter of the COL1A1 gene into worm-infected mice suppressed TGF-beta1, COL1A1, tissue inhibitor of metalloproteinase-1, and decreased COL3A1 mRNAs to a lesser extent. Sequence comparisons within the mouse genome found homologous sequences within the COL3A1, TGF-beta1, and TIMP-1 5' flanking regions. Cold competition gel mobility shift assays using these homologous sequences with 5' and 3' flanking regions found in the natural COL1A1 gene showed competition. Competitive gel mobility assays in a separate experiment showed no competition using a 5-base mutated or scrambled sequence. Explanted liver granulomas from saline-injected mice incorporated 10.45 +/- 1.7% (3)H-proline into newly synthesized collagen, whereas decoy-treated mice showed no collagen synthesis. Compared with the saline control schistosomiasis mice phosphorothioate double-stranded oligodeoxynucleotide treatment decreased total liver collagen content (i.e. hydroxy-4-proline) by 34%. This novel molecular approach has the potential to be employed as a novel antifibrotic treatment modality.
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PMID:A novel nonsteroidal antifibrotic oligo decoy containing the TGF-beta element found in the COL1A1 gene which regulates murine schistosomiasis liver fibrosis. 1588 Mar 83

The disease manifestations of schistosomiasis arise from the mammalian host-mediated type 2 T-helper cell-induced (Th2) fibro-granulomatous inflammatory response to eggs trapped within host tissues. Activated hepatic stellate cells are well described as the effector cells of hepatic fibrosis in a variety of human diseases and rodent models. The aim of this study was to further understand the mechanism of fibrosis and the role of hepatic stellate cells in hepatic schistosomiasis progression. Groups of female CBA mice, which produce an intermediate degree of Schistosoma japonicum-induced liver fibrosis, were infected with S. japonicum, perfused at fortnightly time points and the liver tissue and contained egg granulomas examined by immunohistochemistry and cytokine and chemokine analysis using quantitative PCR. Immunohistochemistry demonstrated the presence of activated hepatic stellate cells in the periphery of egg granulomas, adjacent to fibrotic areas. Time course analysis demonstrated that the transcription of smooth muscle actin-alpha type 1 collagen, IL-4, IL-13, IL-13Ralpha2 and tissue inhibitor of metalloproteinase-1 mirrored the initial increase and subsequent down-modulation of granuloma diameter in mice. However, the transcription of monocyte chemo-attractant protein-1, Regulated upon Activation Normal T Cell Expressed and Secreted (RANTES), TNF-alpha, IFN-gamma and matrix metalloproteinase-9 paralleled the evolution of the total liver disease burden. Transforming growth factor-beta1 transcription did not appear to be of biological significance in this mouse model. Immunohistochemical analysis of human hepatic granulomas showed close association of smooth muscle actin-alpha-expressing cells with fibrosis in five available cases of end-stage (advanced) schistosomiasis japonica. We conclude that activated hepatic stellate cells play a contributory role in the granulomatous, fibrotic process induced by S. japonicum eggs, both in the murine model and in human disease.
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PMID:A contributory role for activated hepatic stellate cells in the dynamics of Schistosoma japonicum egg-induced fibrosis. 1680 22


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