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:3.1.26.9 (ribonuclease)
6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now widely accepted that the mammary gland is under interconnected hormonal and local control. Growth factors are involved in the intercellular signalling of the gland. Our aim was the detection of transforming growth factors alpha (TGF-alpha) and beta 1 (TGF-beta 1) messenger RNA during mammogenesis, lactogenesis, galactopoiesis and involution in the bovine mammary gland (total n = 27). During these stages the RNA was assessed by means of ribonuclease protection assay and reverse transcription-polymerase chain reaction (RT-PCR). To study possible influences of oestrogen, progesterone and prolactin on growth factor expression, mammary RNA was obtained from heifers after induced mammogenesis and lactogenesis, with and without additional prolactin inhibition (total n = 20). Very low levels of TGF-alpha and TGF-beta 1 expression were detected during lactogenesis and galactopoiesis, increasing levels during mammogenesis of primigravid heifers, and highest levels during mammogenesis of virgin heifers and during involution. TGF-alpha expression after induced mammogenesis was greater than after induced lactogenesis or physiological mammogenesis during pregnancy. Furthermore, TGF-alpha mRNA contents increased after prolactin inhibition. TGF-beta 1 expression was almost equal after induced mammogenesis and lactogenesis, but greater than during the physiological mammogenesis and lactogenesis. In conclusion, it can be assumed that growth promoting TGF-alpha and growth inhibiting TGF-beta 1 are co-expressed in the bovine mammary gland. Higher mRNA contents of both factors during mammogenesis and involution may indicate autocrine or paracrine functions for these growth factors during proliferation and reorganisation of the mammary tissue.
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PMID:Expression of transforming growth factors alpha and beta-1 messenger RNA in the bovine mammary gland during different stages of development and lactation. 948 95

Localization of tenascin-C in vivo and cell culture experiments in vitro have provided evidence for stromal production of tenascin-C in malignant tumors of a variety of organs. Here we raised the question of whether the mesenchymal stroma in the case of endometrial adenocarcinoma is the unique source of tenascin-C. Therefore, the expression of tenascin-C mRNA by human endometrial adenocarcinoma cells and endometrial stroma cells was investigated. Several preparations of endometrial stroma cells produced tenascin-C mRNA. Using a serum-free defined cell culture medium, production of tenascin-C mRNA could be increased by adding either serum or 20 ng TGF-beta/mL to the cell culture medium. Reverse transcriptase polymerase chain reaction analysis revealed that five out of six endometrial adenocarcinoma cell lines produced tenascin-C mRNA. Northern blot experiments and ribonuclease protection assays provided evidence that the number of copies of tenascin-C mRNA was small. Analysis of expressed splice variants by reverse transcriptase polymerase chain reaction analysis revealed the abundance of one major splice variant that lacked all potential alternatively spliced fibronectin type-III-like repeats. Regarding larger splice variants, all fragment sizes that could theoretically originate from seven alternatively spliced fibronectin type-III-like repeats were observed. Evaluating relative signal intensities, the splice variants containing a single fibronectin type-III-like repeat and the variant possessing all but one alternatively spliced repeats were most frequent. In summary, evidence is provided that tenascin-C can originate from both tissue compartments of the human endometrium stroma and (tumor) epithelium. Splice variant analysis revealed a high number of splice variants and a relative high proportion of variants that have so far been regarded as minor constituents of expressed tenascin-C.
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PMID:Expression of tenascin-C by human endometrial adenocarcinoma and stroma cells: heterogeneity of splice variants and induction by TGF-beta. 959 65

Microglia are the resident macrophages of the brain, and when activated, have functions including cytokine production, phagocytosis and antigen presentation. The class II MHC genes encode proteins that present antigenic peptides to helper T cells, leading to T cell activation and the development of an antigen-specific immune response. Class II MHC gene expression is strictly regulated by the class II transactivator (CIITA) transcription factor. In this study, we investigated the effects of various immunomodulatory cytokines on IFN-gamma induction of class II MHC and CIITA gene expression in microglia, both primary microglia and a murine microglial cell line, EOC 20. By flow cytometry analysis we show that IFN-gamma-induced surface expression of class II MHC molecules on EOC 20 cells can be inhibited by the cytokines TGF-beta1, IL-4 and IL-10, but not IL-13. Using a ribonuclease protection assay, we have found that TGF-beta1, IL-4 and IL-10 act by inhibiting the expression of IFN-gamma-induced CIITA mRNA and, in turn, class II MHC mRNA. TGF-beta1, IL-4, and IL-10 inhibition of IFN-gamma-induced CIITA mRNA accumulation was not due to destabilization of CIITA mRNA, suggesting an effect at the level of transcription. In primary murine microglia, IL-10 and TGF-beta1 inhibited IFN-gamma-induced CIITA and class II MHC expression. However, a discordant effect of IL-4 was noted in that IL-4 enhanced IFN-gamma-induced CIITA and class II MHC expression in primary microglia. Although some differences are observed between EOC 20 cells and primary microglia in terms of responsiveness to TGF-beta, IL-4 and IL-10, CIITA and class II MHC gene expression are coordinately modulated.
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PMID:Class II transactivator and class II MHC gene expression in microglia: modulation by the cytokines TGF-beta, IL-4, IL-13 and IL-10. 1022 95

Aqueous humor (AqH) contains immunosuppressive factors, especially TGF-beta2, that contribute to the immune privileged status of the anterior chamber. However, this may not be true when the blood-ocular barrier is compromised by ocular inflammation. To determine the immunosuppressive status of AqH from murine eyes afflicted with experimental autoimmune uveitis, B10.A mice were immunized with interphotoreceptor retinoid-binding protein. AqH was collected from eyes of affected mice periodically after immunization and then evaluated for content of TGF-beta, proinflammatory cytokines, and the capacity to suppress anti-CD3-driven T cell proliferation. mRNA expression of selected cytokines in iris and ciliary body from inflamed eyes was analyzed by ribonuclease protection assay. We found that TGF-beta levels were significantly increased in AqH from EAU eyes on days 11, 17, and 28. AqH collected on day 11 (onset of disease) failed to suppress T cell proliferation and contained large amounts of locally produced IL-6 that antagonized TGF-beta. In contrast, AqH collected at 17 days (when ocular inflammation was progressively severe) re-expressed the ability to suppress T cell proliferation, in this case due to high levels of blood-derived TGF-beta1 and eye-derived TGF-beta2 in the absence of IL-6. Thus, during the onset of experimental autoimmune uveitis, the ocular microenvironment loses its immunosuppressive properties due to local production of IL-6. But as inflammation mounts, AqH IL-6 content falls, and the fluid reacquires sufficient TGF-beta eventually to suppress immunogenic inflammation. The paradoxical roles of IL-6 in antagonizing TGF-beta, while promoting TGF-beta accumulation during ocular inflammation, is discussed.
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PMID:Analysis of immunomodulatory activities of aqueous humor from eyes of mice with experimental autoimmune uveitis. 1064 Jul 29

Interferon-gamma-inducible 10 kd protein (IP-10) is an ELR (Glu-Leu-Arg)(-) alpha chemokine with known chemotactic effects on T cells and monocytes, as well as anti-viral, anti-angiogenic, and anti-tumor effects. Previous studies have demonstrated that in cultured rat astrocytes and microglia, stimulation with LPS or virus can induce the expression of IP-10. In this study, we determined the pattern of IP-10 gene induction in primary human microglia and astrocytes by cytokines and LPS using ribonuclease protection assay. The expression of IP-10 mRNA was compared with that of other alpha (IL-8) and beta chemokines. The results showed that in human microglia, IP-10 expression was induced equally potently by LPS, IFNbeta or IFNgamma. "Proinflammatory" cytokines IL-1beta or TNFalpha also induced small amounts of IP-10 mRNA. "Anti-inflammatory" cytokines IL-4, IL-10 and TGFbeta were ineffective in inducing IP-10 in microglia. In human astrocytes, induction of IP-10 mRNA by cytokines was similar to that in microglia. LPS, however, was ineffective in inducing IP-10 in human astrocytes. The monocyte chemoattractant beta-chemokine I-309 mRNA was induced in human astrocytes and microglia by IFNbeta or IFNgamma, or by LPS in microglia, showing a tight co-regulation with IP-10 mRNA expression. In contrast to the potent induction of IP-10 and I-309 by IFNs in human glia, the ELR(+) alpha chemokine IL-8 mRNA was induced by IL-1beta and TNFalpha, and to a lesser extent by IFNbeta in microglia. IFNbeta but not IFNgamma was effective in inducing the expression of beta chemokines MIP-1alpha and MIP-1beta in human microglia, with the levels of mRNA similar to those induced by IL-1beta or TNFalpha. Neither MIP-1alpha nor MIP-1beta mRNAs were induced by any stimulation in human astrocytes. The induction of RANTES mRNA in microglia by IFNbeta, IL-1beta or TNFalpha was variable, showing no to low level expression depending on the case, whereas LPS provided a consistent inducing signal. In astrocytes, only cytokine combinations (IFN + IL-1beta) effectively induced the RANTES mRNA. These results demonstrate that distinct sets of chemokine genes are induced in human glial cells by cytokines and interferons. These results may have wide implications for inflammatory, vascular and neoplastic diseases of the CNS.
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PMID:Distinct patterns of stimulus-inducible chemokine mRNA accumulation in human fetal astrocytes and microglia. 1069 46

The purpose of these studies was to examine the role of cytokines in the pathogenesis of cisplatin nephrotoxicity. Injection of mice with cisplatin (20 mg/kg) led to severe renal failure. The expression of cytokines, chemokines, and ICAM-1 in kidney was measured by ribonuclease protection assays and RT-PCR. We found significant upregulation of TNF-alpha, TGF-beta, RANTES, MIP-2, MCP-1, TCA3, IL-1beta, and ICAM-1 in kidneys from cisplatin-treated animals. In addition, serum, kidney, and urine levels of TNF-alpha measured by ELISA were increased by cisplatin. Inhibitors of TNF-alpha production (GM6001, pentoxifylline) and TNF-alpha Ab's reduced serum and kidney TNF-alpha protein levels and also blunted the cisplatin-induced increases in TNF-alpha, TGF-beta, RANTES, MIP-2, MCP-1, and IL-1beta, but not ICAM-1, mRNA. In addition, the TNF-alpha inhibitors also ameliorated cisplatin-induced renal dysfunction and reduced cisplatin-induced structural damage. Likewise, TNF-alpha-deficient mice were resistant to cisplatin nephrotoxicity. These results indicate cisplatin nephrotoxicity is characterized by activation of proinflammatory cytokines and chemokines. TNF-alpha appears to play a central role in the activation of this cytokine response and also in the pathogenesis of cisplatin renal injury.
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PMID:TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. 1223 3

Transforming growth factor (TGF)-beta1 and a number of TGF-beta-responsive genes are transiently enhanced following induction of ischemic acute renal failure (ARF) in the rat. The mRNA and protein expression of TGF-beta receptors were analyzed in postischemic rat kidneys by ribonuclease protection, in situ hybridization, and immunohistochemistry. TGF-betaRI and -RII were enhanced within 3 days of ischemia-reperfusion (I/R) injury and remained elevated for up 7 days post-I/R; TGF-beta receptor expression was localized primarily in regenerating tubules within the outer medulla. A neutralizing TGF-beta antibody exacerbated cellular proliferation observed on day 3 postischemia but had no effect on day 1 or 2. TGF-beta antibody treatment had no measurable effect on loss of renal function or the restoration of renal function during the recovery response for up to 35 days postsurgery. However, ischemic injury resulted in modest renal hypertrophy that is due, in part, to in an increase in the number of interstitial cells in the postischemic kidney. Immunohistochemistry showed that several of these cells stained positively for the fibroblast-specific marker, S100A4 positive. Anti-TGF-beta treatment substantially attenuated the renal hypertrophy, interstitial cellularity, and S100A4-positive cells present at 35 days post-I/R. Finally, TGF-beta immunoneutralization attenuated the loss of renal vascular density following recovery from I/R injury. These data suggest that the TGF-beta/TbetaR system is enhanced in the postischemic kidney. However, the current study failed to identify a prominent role for this system in the repair of proximal tubules following ARF. In contrast, the activation of this system may play an important role in the long-term structure of the postischemic kidney by influencing microvascular structure and interstitial cellularity.
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PMID:Transforming growth factor-beta in acute renal failure: receptor expression, effects on proliferation, cellularity, and vascularization after recovery from injury. 1553 65

Arrestins and G proteins-coupled receptor kinases (GRKs) regulate signaling and trafficking of G protein-coupled receptors. We investigated changes in the expression of arrestins and GRKs in the striatum of patients with Parkinson's disease without (PD) or with dementia (PDD) at postmortem using Western blotting and ribonuclease protection assay. Both PD and PDD groups had similar degree of dopamine depletion in all striatal regions. Arrestin proteins and mRNAs were increased in the PDD group throughout striatum. Protein and mRNA of GRK5, the major subtype in the human striatum, and GRK3 were also upregulated, whereas GRK2 and 6 were mostly unchanged. The PD group had lower concentration of arrestins and GRKs than the PDD group. There was no statistical link between the load of Alzheimer's pathology and the expression of these signaling proteins. Upregulation of arrestins and GRK in PDD may confer resistance to the therapeutic effects of levodopa often observed in these patients. In addition, increased arrestin and GRK concentrations may lead to dementia via perturbation of multiple signaling mechanisms.
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PMID:Arrestins and two receptor kinases are upregulated in Parkinson's disease with dementia. 1712 86


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