Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory bowel disease (IBD) is associated with Th1/Th2 cytokine dysregulation, leukocyte extravasation, and tissue edema, but the mechanisms for cytokine-mediated vascular dysfunction are not understood. To investigate how cytokines might control edema in IBD, we determined vascular permeability and IFN-gamma expression in two models of murine colitis: SCID mice reconstituted with CD45RB(high T-lymphocytes (CD45RB(high)/SCID mice), and interleukin-10 gene deficient (IL-10(-/-)) mice. We also investigated the in vitro effects of IFN-gamma and IL-10 on human endothelial solute barrier and junction protein expression. Vascular permeability in CD45RB(high)/SCID and IL-10(-/-) mice was quantified using tissue (131)I-IgG accumulation. The IFN-gamma message was quantified using the ribonuclease protection assay. Endothelial barrier integrity in vitro was measured by transmonolayer electrical resistance, and junctional proteins were examined by immunoblotting and fluorescence microscopy. Both CD45RB(high)/SCID and IL-10(-/-) mice exhibit enhanced colonic microvascular leakage and IFN-gamma message levels compared to their respective controls. In vitro, IFN-gamma also reduced endothelial barrier (monolayer electrical resistance, increased albumin permeability) and reduced tight junction (occludin) expression and staining. These effects were reversed by pretreatment of monolayers with IL-10. Therefore, in vivo IFN-gamma and IL-10 may modulate microvascular leakage in IBD partly by controlling the expression of intestinal endothelial tight junctional proteins.
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PMID:Interferon-gamma and interleukin-10 reciprocally regulate endothelial junction integrity and barrier function. 1116 3

To evaluate the immunomodulatory effects of histamine in vivo, we analyzed an experimental syngenic tumor model using a colon adenocarcinoma cell line, CT-26, in Balb/c mice. In this model, distinct tumor growth was observed around 6 days after inoculation. Daily administration of cimetidine (0.12 mg/kg/day) significantly suppressed the increases in tumor volume and weight. On day 6 and day 7, histidine decarboxylase (HDC) activity was markedly increased. To examine the alterations in the local immune system, the cytokine expressions in the tumor tissue were measured by ribonuclease protection assay. The cytokine expression levels such as lymphotoxin-beta, tumor necrosis factor-alpha, interferon-gamma, interleukin-10, and interleukin-15 were considerably lower in tissues on day 14 than those on day 6. These decreased expressions were all restored by cimetidine. These results indicated that the effects of cimetidine on tumor growth in this model might be mediated by restoration of the decreased local cytokine expression, which exerts antitumoral effects.
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PMID:Effect of cimetidine on intratumoral cytokine expression in an experimental tumor. 1124 50