Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 situ hybridization was used to demonstrate serum amyloid A (SAA) gene expression in arthritic joint tissue from lentivirus-infected sheep and goats. SAA gene transcription occurs in isolated individual synovial cells and occasional giant cells but not in uninfected or uninflamed synovial tissue. These findings support the notion (derived from in vitro observations) that at least one member of the SAA gene/protein family may function as an autocrine collagenase inducer in inflammatory arthritis. Since we used heterologous DNA probes derived from human clones, our findings also support the growing evidence for interspecies conservation of SAA genes.
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PMID:Serum amyloid A gene transcription in synovial cells during retroviral arthritis. 151 61

We report that nucleic acid sequence analysis of a full-length cDNA clone for a rabbit serum amyloid A (SAA)-like protein has identified this protein as more closely related to SAA3 than to SAA1. SAA3 induced collagenase synthesis in rabbit synovial fibroblasts, and immune IgG raised against this SAA protein abrogated the induction. Using antisera to immunoprecipitate biosynthetically labeled 3H-SAA and 3H-collagenase from culture medium, we compared the levels of SAA and collagenase synthesized by cultures of rabbit fibroblasts at early passage (passages 3-6) with those synthesized by late passage cells (passage 16). Comparatively high levels of both proteins were produced constitutively by fibroblasts at low passage. With increasing passage, levels of both proteins drop so that by passage 16, constitutive production of SAA and collagenase was only approximately 15-20% that of passage 3 cells. Cells at low passage could be readily stimulated with phorbol myristate acetate (PMA) or interleukin 1 (IL-1) to synthesize increased amounts of both SAA and collagenase. In passage 5 cells treated with PMA, we detected increased SAA mRNA by 1.5 h and collagenase mRNA by 5 h. However, older passage cells were more refractory to stimulation and required longer induction times. We suggest that SAA3 may be expressed by fibroblasts at sites of acute inflammation or injury, and that elevated levels of SAA3 may signify "activated" fibroblasts which are already producing increased amounts of collagenase constitutively and which are predisposed to further stimulation.
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PMID:Serum amyloid A (SAA3) produced by rabbit synovial fibroblasts treated with phorbol esters or interleukin 1 induces synthesis of collagenase and is neutralized with specific antiserum. 184 44

Interleukin-1 (IL-1) is secreted by macrophages, macrophage-like cells (e.g. Langerhans cells) and by astrocytes, keratinocytes, fibroblasts or natural killer cells. IL-1 is directly involved in the activation of helper T lymphocytes. However, it has been shown that IL-1 also induces release of collagenase and prostaglandins by fibroblasts. Furthermore, injections of IL-1 into animals are followed by fever, leukocytosis, increased serum concentrations of fibrinogen, serum amyloid A and haptoglobin, and decreased levels of iron and zinc. IL-1 has been extracted from experimental granuloma and from tissues of animals with endotoxinemia. Synovial fluids from patients with osteoarthritis contain significant amounts of IL-1. All in all, IL-1 may be ultimately involved in the development of fever and fibrosis, in the destruction of joints and the activation of T lymphocytes during inflammatory processes.
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PMID:[Interleukin 1]. 241 45

Two autocrine proteins of 14 and 12 kilodaltons that induce the synthesis of rabbit fibroblast collagenase were identified. The proteins were purified from serum-free culture medium taken from rabbit synovial fibroblasts stimulated with phorbol myristate acetate. The amino-terminal sequences of the 14- and 12-kilodalton species were approximately 60 to 80 percent homologous with serum amyloid A and beta 2 microglobulin, respectively. The polyacrylamide gel-eluted proteins retained the ability to induce collagenase synthesis in rabbit and human fibroblasts. These autocrine proteins may provide a means to modulate collagenase synthesis in normal remodeling as well as in inflammation and disease states.
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PMID:Autocrine induction of collagenase by serum amyloid A-like and beta 2-microglobulin-like proteins. 268 25

We have determined the genomic sequence of the human GSAA1 gene, a member of the family of acute-phase human serum amyloid A (SAA)-encoding genes. This sequence predicts a mature protein of 104 amino acids (aa), several of which differ from residues usually conserved in the sequence of SAA proteins isolated from serum. Despite coding differences, however, the four-exon structure of GSAA1 resembles that of other SAA genes in humans and mice. The N-terminal 25 aa of the mature GSAA1 protein are virtually identical to those of an 'SAA-like' autocrine collagenase inducer produced by rabbit synovial fibroblasts; the latter also differ from the corresponding aa found in SAA in serum. We propose that GSAA1 is the human gene coding for a protein closely related to the SAA, but which is adapted to this important autocrine cytokine function.
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PMID:The human serum amyloid A (SAA)-encoding gene GSAA1: nucleotide sequence and possible autocrine-collagenase-inducer function. 255 75

Interleukin 1, or IL 1, otherwise known as lymphocyte-activating factor, is a macrophage-derived 12,000- to 15,000-dalton polypeptide. Isoelectric focusing of human IL 1 reveals three peaks at pI's of 5.2, 6.0 and 6.9 respectively. IL 1 can be depleted of lymphocyte-derived IL 2 by SP-Sephadex chromatography. IL 1 augments the mitogenic response of PNA- Lyt 1+ thymocytes, and promotes thymocyte helper functions and B cell antibody production. IL 1 induces stable E rosette formation and the production of lymphokines such as T cell growth factor (IL 2) by peripheral T lymphocytes. Others have shown that IL 1 or closely related factors also stimulate hypothalamic cells to induce fever; induce in vitro fibroblast growth, prostaglandin, and collagenase production; and stimulate hepatocytes to produce acute phase proteins such as serum amyloid A. Murine epidermal cells also produce a 15,000-dalton factor that is mitogenic for thymocytes and may be similar to IL 1. We have recently hybridized spleen cells from mice sensitized with partially purified human IL 1 with a myeloma cell line. Clones have been isolated that produce supernatants that partially inhibit the thymocyte proliferative response to IL 1 but not the T cell growth factor activity of IL 2. Should these hybridoma products prove to be monoclonal anti-IL 1 antibodies, they will facilitate the further purification and characterization of IL 1.
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PMID:Lymphokines: their role in lymphocyte responses. Properties of interleukin 1. 680 Aug 41

Regulation of the in vitro synthesis of the serum amyloid proteins A and P has been studied with hepatocyte cultures from CBA/J and C3H/HeJ mice. Liver cells were isolated by the collagenase perfusion technique and established for 48 h in the presence of fetal calf serum. Viable cells could then be maintained in the absence of serum for at least 72 h and in the presence of serum for up to 2 weeks. Serum amyloid A synthesis differed from serum amyloid P synthesis in three significant ways. 1) Serum amyloid A production was stimulated in the presence of fetal calf serum, whereas serum amyloid P was not; 2) serum amyloid A synthesis was increased 200% by monokine-rich macrophage supernatants while serum amyloid P was increased only 10 to 20%; 3) serum amyloid A synthesis was strikingly resistant to cycloheximide inhibition as compared with serum amyloid P and other liver proteins. It is concluded that the in vivo asynchrony of the acute phase serum amyloid A and serum amyloid P responses results at least in part from differences in regulatory mechanisms for their synthesis by hepatocytes.
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PMID:Different regulatory mechanisms for serum amyloid A and serum amyloid P synthesis by cultured mouse hepatocytes. 685 23

We found that the matrix metalloproteinases collagenase (MMP-1) and stromelysin (MMP-3) each has the ability to degrade a novel substrate, serum amyloid A (SAA3). SAA3 is a product of rabbit synovial fibroblasts stimulated with phorbol esters or interleukin-1, and it acts in an autocrine or paracrine manner to induce collagenase in both rabbit and human fibroblasts. Recombinant rabbit fibroblast procollagenase and human fibroblast prostromelysin were produced by baby hamster kidney (BHK) cells stably transfected with these genes, and latent enzyme was activated with aminophenylmercuric acetate (APMA). The Km for both enzymes was approximately 10 microM, and the Vmax for collagenase was approximately 6 pmol/minute/100 ng enzyme, while that for stromelysin was about 3-fold faster. Treatment of SAA3 with either enzyme generated a fragment of approx. 6 kDa that has the same amino terminus as the parent molecule, but this fragment was rapidly degraded. We have been unable to isolate C-terminal fragments, suggesting that the mature protein is cleaved at multiple sites and/or that the initial cleavage fragment is readily digested. The amino acid composition of the 6 kDa fragment suggests that the 14 kDa protein is cleaved at residues 50-57, a hydrophobic region that is conserved between rabbit SAA3 and human SAA1. We conclude that the ability of collagenase and stromelysin to degrade SAA3 broadens the repertoire of substrates for these matrix degrading enzymes, and we speculate that the presence of a feedback mechanism that can subvert the autocrine/paracrine stimulation of matrix-degrading enzymes may play a role in limiting matrix degradation during inflammatory conditions.
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PMID:The acute phase reactant serum amyloid A (SAA3) is a novel substrate for degradation by the metalloproteinases collagenase and stromelysin. 846 13

The serum amyloid A (SAA) protein has been implicated in the progression and pathogenesis of rheumatoid arthritis through induction of collagenase activity in synovial fibroblast cells that line the joint tissues. We demonstrate that SAA is synergistically induced in synovial cells by interleukin (IL)-1 and IL-6 that are present at significantly high level in the synovial fluid of arthritis patients. These cytokines induced phenotypic changes in synovial cells, promoting protrusion and increased cellular contact. Induction of SAA under this condition is mediated by promoter elements located between -254 and -226, which contains binding sites for transcription factors Sp1 and SAA activating sequence binding factor (SAF). Mutation of these sequences abolishes SAA promoter response to IL-1 and IL-6. The role of Sp1 in SAA induction was demonstrated by increased DNA binding activity, phosphorylation, and increased protein content of Sp1 during cytokine treatment. Sp1 interacts with the SAA promoter in association with SAF as an SAF. Sp1 heteromeric complex. Furthermore, using a phosphatase inhibitor, we demonstrated increased transactivation potential of both Sp1 and SAF as a consequence of a phosphorylation event. These results provide first evidence for cytokine-mediated activation of Sp1 in synovial fibroblast cells and its participation in regulating SAA expression by acting in conjunction with SAF.
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PMID:Activation of Sp1 and its functional co-operation with serum amyloid A-activating sequence binding factor in synoviocyte cells trigger synergistic action of interleukin-1 and interleukin-6 in serum amyloid A gene expression. 993 31

The systemic response to endotoxin is characterized by hypotension and severe reductions in blood pressure, leading to cardiovascular collapse that can accompany septicemia. The renin/angiotensin system would normally be expected to respond to hypotensive challenge; however, inflammation appears to modify this response. This study identifies a strong acute phase response of the kidney that is characterized by enhanced expression of serum amyloid A, haptoglobin and tissue inhibitor for metalloproteinase-1 and a reduced expression of renin. Equivalent regulatory effects were observed for the immortalized As4.1 kidney cell line that models certain features of juxtaglomerular cells. Oncostatin M, a known endotoxin-responsive proinflammatory cytokine, proved to be an effective inhibitor of renin gene expression. Suppression by oncostatin M involves activated STAT5 and requires an inhibitory element in the renin promoter that functions separately from cell type-specific enhancer elements. The renal acute phase reaction, unlike the liver acute phase reaction, is more strongly dependent on locally produced inflammatory factors.
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PMID:Endotoxin-induced renal inflammatory response. Oncostatin M as a major mediator of suppressed renin expression. 1080 9


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