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)

To clarify the role of intercellular communication in the liver during accumulation of neutrophils, the release of cytokine-induced neutrophil chemoattractant (CINC) (interleukin-8 [IL-8] related protein in rodents) by hepatocytes was investigated in the presence of Kupffer cell-conditioned medium in vitro. Kupffer cells were prepared by perfusion of rat liver with collagenase followed by centrifugation on a metrizamide gradient and were cultured in the presence or absence of lipopolysacharide (LPS). The conditioned medium was collected after 24 hours, and rat hepatocytes were cultured in the presence or absence of Kupffer cell-conditioned medium. An amount of CINC in the culture supernatant was measured by western blotting analysis and enzyme-linked immunosorbent assay (ELISA), and expression of its messenger RNA (mRNA) was assessed by the polymerase chain reaction. LPS-stimulated Kupffer cell-conditioned medium enhanced an expression of CINC mRNA in hepatocytes and increased the production of CINC by hepatocytes. Enhanced production of CINC was not shown when the Kupffer cell-conditioned medium was pretreated with heat (56 degrees C, 30 minutes). The production of CINC by hepatocytes in the presence of the LPS-stimulated Kupffer cell-conditioned medium was reduced by an antibody against interleukin 1 beta (IL-1 beta), but not by antibodies against tumor necrosis factor alpha (TNF-alpha) or LPS. These results suggest that production of CINC by hepatocytes could be regulated by IL-1 beta released from Kupffer cells, leading to neutrophil accumulation during liver injury, because this protein is a strong chemoattractant for neutrophils.
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PMID:Cytokine-induced neutrophil chemoattractant release from hepatocytes is modulated by Kupffer cells. 859 63

Increasing evidence suggests that cytokine products of the immune system may play a regulatory role in corpus luteum regulation in several species. The role of cytokines in primate luteal function, however, remains unclear. In the present study we examined the effects of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interferon-gamma (IFN-gamma) on progesterone and prostaglandin (PGE2, PGF2 alpha) production by primate luteal cells in vitro. Specifically, corpora lutea were removed from normally cycling cynomolgus monkeys (n = 30 corpora lutea) during either the early (Days 3-5 after the estimated LH surge), mid (Days 8-10), or late (Days 12-14) luteal phase of the menstrual cycle. The corpora lutea were dispersed into individual cells using collagenase, DNase, and hyaluronidase. Approximately 50,000 viable luteal cells per tube were incubated in Ham's F-10 medium with increasing concentrations of IL-1 beta (0.1-10 ng/ml), TNF alpha (1-100 ng/ml), or IFN-gamma (10-1000 U/ml) in the presence and absence of hCG for 8 h at 37 degrees C. TNF alpha and IFN-gamma had no effect on progesterone PGE2, or PGF2 alpha production during any phase of the cycle at the doses tested. In contrast, IL-1 beta significantly stimulated PGF2 alpha production in a dose-dependent manner during the mid and late luteal phases (p < 0.05). Human CG alone had no effect on PGE2 or PGF2 alpha production by dispersed luteal cells in vitro but inhibited IL-1 beta-stimulated PGF2 alpha production. As expected, hCG stimulated progesterone production by primate luteal cells in vitro. Interestingly, IL-1 beta inhibited this hCG stimulation of progesterone production. In summary, these date suggest that IL-1 beta is a potentially important modulator of prostaglandin production by the primate corpus luteum. In view of this, cytokine-mediated changes in prostaglandin production by the primate corpus luteum may participate in the physiological regulation of luteal function.
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PMID:Interleukin-1 beta modulates prostaglandin and progesterone production by primate luteal cells in vitro. 904 11

Chronically sun-damaged human skin has a wrinkled, aged appearance as a result of alterations in the dermal extracellular matrix. Secondary effectors such as cytokines and integrins may mediate the effects of UV radiation on the skin by regulating the synthesis of metalloproteinases and structural proteins including collagen. The aim of this study was to semi-quantify the steady-state mRNA levels of interleukin-1 alpha, tumor necrosis factor alpha, transforming growth factor beta, collagenase, stromelysin, collagen, and integrins (alpha, and alpha2) in the skin of hairless mice that were either treated with UV or concurrently treated with UV and topical tretinoin for 5 weeks. Total RNA was extracted from the skin of the mice, reverse transcribed to cDNA, and amplified by the polymerase chain reaction in the presence of 32P-dCTP using gene-specific primers. Results were normalized relative to glyceraldehyde-3-phosphate dehydrogenase levels. Steady-state mRNA levels of the cytokines and integrins were increased by UV radiation. Concurrent UV and topical tretinoin treatment superinduced the expression of interleukin-1, increased alpha 1, and decreased alpha 2 integrin expression. Immunofluorescence analysis showed increased dermal localization of beta 1 integrin in UV and tretinoin treated skin. These results suggest that cytokines and integrins may be involved in the mechanism of photo-damage.
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PMID:Ultraviolet B radiation increases steady-state mRNA levels for cytokines and integrins in hairless mouse skin: modulation by topical tretinoin. 955 89

Endometrial matrix metalloproteinases (MMPs), which increase dramatically at menstruation, are purported to cause the focal tissue breakdown at menstruation, but how their expression or activation is locally regulated is unknown. Mast cell activation occurs within perimenstrual endometrium, and we postulated that mast cell products would regulate endometrial MMPs. We have examined the interaction between human mast cells and endometrial stromal cells with regard to MMP production and activation. The human mast cell line (HMC-1) in coculture with stromal cells stimulated stromal cell proMMP-1 and proMMP-3, and to a lesser extent proMMP-2 production, with increasing stimulation as mast cell number increased. Mast cell-conditioned medium also increased both protein and mRNA for stromal proMMP-1 and proMMP-3, this being abrogated by preadsorption of mast cell-conditioned medium with antisera to interleukin-1 and tumor necrosis factor alpha. Mast cell-conditioned medium added to stromal cell culture medium in vitro along with added heparin (which stabilizes tryptase activity) resulted in the appearance of molecular weight forms indicative of active MMP-3 and MMP-1. Thus activated mast cells within the endometrium prior to menstruation have the potential to stimulate MMP production by endometrial stromal cells and to initiate precursor activation, and are likely to account for the local nature of endometrial MMP action resulting in foci of tissue breakdown at menstruation.
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PMID:Mast cell regulation of human endometrial matrix metalloproteinases: A mechanism underlying menstruation. 971 71

Disruption of the balance between proteases and protease inhibitors is often associated with pathologic tissue destruction. To explore the therapeutic potential of secretory leukocyte protease inhibitor (SLPI) in erosive joint diseases, we cloned, sequenced, and expressed active rat SLPI, which shares the protease-reactive site found in human SLPI. In a rat streptococcal cell wall (SCW)-induced model of inflammatory erosive polyarthritis, endogenous SLPI was unexpectedly upregulated at both mRNA and protein levels in inflamed joint tissues. Systemic delivery of purified recombinant rat SLPI inhibited joint inflammation and cartilage and bone destruction. Inflammatory pathways as reflected by circulating tumor necrosis factor alpha and nuclear factor kappaB activation and cartilage resorption detected by circulating levels of type II collagen collagenase-generated cleavage products were all diminished by SLPI treatment in acute and chronic arthritis, indicating that the action of SLPI may extend beyond inhibition of serine proteases.
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PMID:Secretory leukocyte protease inhibitor suppresses the inflammation and joint damage of bacterial cell wall-induced arthritis. 1044 24

We showed previously that human malignant non-Hodgkin's lymphomas (NHL) degrade extracellular matrix (ECM) components through the action of metalloproteinases and that elevated expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) correlated with a poor clinical outcome in patients with NHL. In the present study we sought to investigate whether there is any correlation between the expression of gelatinases (MMP-2 and MMP-9), TIMP-1, and the expression of cytokines and growth factors such as interleukin-1beta (IL-1beta), IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGFbeta), and basic fibroblast growth factor (bFGF) in human NHL. In lymphoma tissues obtained from 32 patients, elevated expression of IL-6 correlated significantly with elevated messenger RNA (mRNA) levels of MMP-9, MMP-2, and TIMP-1. Moreover, in human lymphoid cell lines of B- and T-cell origin (Raji, Jurkat, and NC-37), IL-6 stimulated production of MMP-9 and MMP-2 but not TIMP-1. In the Matrigel invasion assay IL-6 significantly upregulated transmigration of Raji and Jurkat cells, which in turn was inhibited by recombinant human TIMP-1 and anti-MMP-9 and MMP-2 antibodies. We postulate that IL-6 may play a role in the clinical aggressiveness of human NHL by stimulating MMP production.
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PMID:Interleukin-6 regulation of matrix metalloproteinase (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression in malignant non-Hodgkin's lymphomas. 1047 38

We have proposed that UV activation of cytokine and integrin signaling pathways may initiate the photoaging process and that one of the effects of tretinoin treatment may be to alter the cytokine and integrin patterns. In previous results, steady-state mRNA levels of interleukin-1alpha, tumor necrosis factor alpha, transforming growth factor beta, collagenase, stromelysin, collagen, and integrins (alpha1 and alpha2) were increased in the skin of hairless mice that were either UV treated or concurrently treated with UV followed by topical tretinoin for 5 weeks. The aim of this study was to focus on the expression of alpha1, alpha2 and alpha5 integrins, IL-1alpha, IL-1beta, cJun, and cFos at an earlier time point (3 weeks). Animals were UV irradiated thrice weekly for 3 weeks and were treated topically with either 0.05% tretinoin or the vehicle immediately after each exposure. Total RNA was prepared and used in RT-PCR with radiolabeled dCTP and specific primers. UV slightly increased steady-state mRNA levels for alpha1, alpha2 and alpha5 integrins whereas UV + tretinoin increased their expression (3-, 2- and 7-fold respectively). Steady-state mRNA levels for IL-1alpha, IL-1beta and cJun were increased with UV (3-, 12- and 6-fold respectively) and with UV + tretinoin (6-, 7- and 9-fold respectively). In contrast, cFos expression was unchanged. In situ staining for IL-1alpha mRNA was slightly more abundant in mice treated for 3 weeks with UV and UV + tretinoin than in controls whereas 5 weeks of UV + tretinoin treatment gave strongly positive staining. Results are consistent with cytokines and integrins mediating the effects of UV on the skin, with modulation of these effects by tretinoin.
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PMID:Steady-state mRNA levels of interleukin-1, integrins, cJun, and cFos in hairless mouse skin during short-term chronic UV exposure and the effect of topical tretinoin. 1054 Sep 44

The present study was performed to evaluate the role of matrix metalloproteinases (MMP) in the pathogenesis of the inflammatory reaction and the development of neuronal injury in a rat model of bacterial meningitis. mRNA encoding specific MMPs (MMP-3, MMP-7, MMP-8, and MMP-9) and the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) were significantly (P < 0.04) upregulated, compared to the beta-actin housekeeping gene, in cortical homogenates at 20 h after infection. In parallel, concentrations of MMP-9 and TNF-alpha in cerebrospinal fluid (CSF) were significantly increased in rats with bacterial meningitis compared to uninfected animals (P = 0.002) and showed a close correlation (r = 0.76; P < 0. 001). Treatment with a hydroxamic acid-type MMP inhibitor (GM6001; 65 mg/kg intraperitoneally every 12 h) beginning at the time of infection significantly lowered the MMP-9 (P < 0.02) and TNF-alpha (P < 0.02) levels in CSF. Histopathology at 25.5 +/- 5.7 h after infection showed neuronal injury (median [range], 3.5% [0 to 17.5%] of the cortex), which was significantly (P < 0.01) reduced to 0% (0 to 10.8%) by GM6001. This is the first report to demonstrate that MMPs contribute to the development of neuronal injury in bacterial meningitis and that inhibition of MMPs may be an effective approach to prevent brain damage as a consequence of the disease.
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PMID:Matrix metalloproteinases contribute to brain damage in experimental pneumococcal meningitis. 1063 24

Collagen synthesis in vascular smooth muscle cells (SMCs) after exposure to tumor necrosis factor alpha (TNF-alpha) was investigated using a culture system. The synthesis of collagenase-digestible proteins (CDP) and noncollagenous proteins (NCP) was evaluated by the [3H]proline incorporation. It was shown that TNF-alpha markedly suppresses the incorporation of [3H]proline into both CDP and NCP in confluent cultures of SMCs but not in sparse cultures of the cells. Such a marked suppression by TNF-alpha was not observed in confluent bovine aortic endothelial cells and human fibroblastic IMR-90 cells. In confluent SMCs, the synthesis of CDP was more strongly inhibited by TNF-alpha than that of NCP. When the CDP synthesis was stimulated by transforming growth factor beta, TNF-alpha suppressed the stimulation in both confluent and sparse SMCs. Human SMCs synthesized types I, III, IV and V collagens; TNF-alpha markedly decreased the relative proportion of types IV and V. It was therefore suggested that TNF-alpha modulates the collagen synthesis by SMCs depending on their cell density and modifies the formation of atherosclerotic lesions.
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PMID:Modulation of collagen synthesis by tumor necrosis factor alpha in cultured vascular smooth muscle cells. 1066 99

We hypothesize that spontaneous regression of corpora lutea (CL) involves short-lasting restructure of luteal tissue with an activation of matrix metalloproteinases (MMPs) and their respective inhibitors (tissue inhibitors of metalloproteinase, TIMPs). This was tested by determining the gene expression of MMP-1, MMP-2, and MMP-9 and respective TIMP-1 and TIMP-2 in luteal tissue from sows at the early, midluteal, and late luteal phase (Days 6-8, Days 9-11, and Days 13-15 of estrous cycle). Gene expression of the three MMPs was low in early, slightly higher in midluteal, and significantly elevated (P < 0.05) in regressing CL. An inverse pattern was found for gene expression of TIMP-1 and TIMP-2. Under culture conditions, the release of MMPs was determined from steroidogenic large luteal cells (LLC). LLC harvested from regressing CL released significantly (P < 0.05) more active MMPs than cells obtained from CL at the early luteal phase. As luteolysis can be induced by prostaglandin F(2alpha) (PGF(2alpha)) and tumor necrosis factor alpha (TNF), we studied their effects on LLC under culture conditions. Treatment of cells with PGF(2alpha) or TNF (10(-7) M or 3 x 10(-9) M, respectively) induced a significantly higher release of MMPs, and gene expression was also significantly stimulated in comparison to that in untreated LLC. The gene expression of TIMPs remained unaffected by either treatment. It is concluded that at the beginning of luteolysis, MMPs are expressed and released in high amounts and that this is essential for the structural regression of the CL.
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PMID:Secretion and gene expression of metalloproteinases and gene expression of their inhibitors in porcine corpora lutea at different stages of the luteal phase. 1077 57


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