Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 57-year-old woman came to our hospital complaining of multiple subcutaneous nodules that developed while she received corticosteroid therapy for pulmonary sarcoidosis. She was treated with interferon-alpha (IFN-alpha) at another hospital for C-type chronic hepatitis and she noticed these nodules with tenderness two months after treatment began. A biopsy specimen of the nodule revealed subcutaneous sarcoid granuloma. Her abnormally high serum-ACE value and subcutaneous nodules resolved after the dose of IFN-alpha was gradually reduced. IFN therapy should be used with care in cases of sarcoidosis in which IFN-gamma and T-lymphocytes are mainly involved.
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PMID:[A case of subcutaneous sarcoid nodules induced by interferon-alpha]. 784 19

The pulmonary granulomatous diseases may be staged using clinical examination, pulmonary function tests, <sup>67</sup>Ga scans, chest X-rays, BAL and serum ACE levels; furthermore, these disorders are clearly associated to changes in lymphocyte subpopulations, CD4+/CD8+ ratio and surface receptors; in particular, T cell activation characterizes early alveolitis phase, while activated macrophages and related cytokines prevail in granulomata and fibrosis development. In this study, we dosed the serum and blood concentrations of IL-6 (a well-known pro-inflammatory cytokine), sIL-2R (marker of T-cell activation), TNF-alpha and IFN-gamma (associated with the granuloma development), in patients affected by active or inactive sarcoidosis, primary tuberculosis, idiopathic pulmonary fibrosis and healthy control subjects, using the ELISA method. Cytokines assay showed significant changes only in subjects with primary tuberculosis and active sarcoidosis; infact, primary tuberculosis was characterized by high values of IL-6 and IFN-gamma both in peripheral blood and in BAL, with high values of sIL-2R in BAL; patients with active sarcoidosis showed high levels of IFN-gamma and TNF-alpha both in BAL and in peripheral blood, associated to an increase of serum sIL-2R levels. Our data confirm that the compared assay of these cytokines in peripheral blood and BAL specimens, may be useful to diagnose and to assess the disease activity in pulmonary granulomatous diseases; in particular, the levels of sIL-2R are a marker of the alveolitis phase, while TNF-alpha and IL-6 levels discriminate patients with sarcoidosis or tuberculosis granulomata, respectively.
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PMID:Cytokines assay in peripheral blood and bronchoalveolar lavage in the diagnosis and staging of pulmonary granulomatous diseases. 1265 92

Severe acute respiratory syndrome (SARS) is a serious and fatal infectious disease caused by SARS coronavirus (SARS-Cov), a novel human coronavirus. SARS-Cov infection stimulates cytokines (e.g., IL-10, IFN-gamma, IL-1, etc.) expression dramatically, and T lymphocytes and their subsets CD4(+) and CD8(+) T cells are decreased after onset of the disease. SARS-specific IgG antibody is generated in the second week and persists for a long time, whereas IgM is expressed transiently. The spike protein and neucleocapsid protein are most abundant in SARS-Cov and contribute dominantly to the antibody production during the course of disease. Spike protein, especially the ACE-2 binding region (318-510aa) is capable of producing neutralizing antibody to SARS-Cov. Neucleocapsid protein induces protective specific CTL to SARS-Cov. Therefore, applications with spike subunit, neucleocapsid subunit as well as inactivated SARS-Cov are three prospective vaccination strategies for SARS.
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PMID:SARS Immunity and Vaccination. 1621 67

We have previously reported that exogenous bradykinin activates immature dendritic cells (DCs) via the bradykinin B(2) receptor (B(2)R), thereby stimulating adaptive immunity. In this study, we show that these premises are met in a model of s.c. infection by Trypanosoma cruzi, a protozoan that liberates kinins from kininogens through its major protease, cruzipain. Intensity of B(2)R-dependent paw edema evoked by trypomastigotes correlated with levels of IL-12 produced by CD11c(+) dendritic cells isolated from draining lymph nodes. The IL-12 response induced by endogenously released kinins was vigorously increased in infected mice pretreated with inhibitors of angiotensin converting enzyme (ACE), a kinin-degrading metallopeptidase. Furthermore, these innate stimulatory effects were linked to B(2)R-dependent up-regulation of IFN-gamma production by Ag-specific T cells. Strikingly, the trypomastigotes failed to up-regulate type 1 immunity in TLR2(-/-) mice, irrespective of ACE inhibitor treatment. Analysis of the dynamics of inflammation revealed that TLR2 triggering by glycosylphosphatidylinositol-anchored mucins induces plasma extravasation, thereby favoring peripheral accumulation of kininogens in sites of infection. Further downstream, the parasites generate high levels of innate kinin signals in peripheral tissues through the activity of cruzipain. The demonstration that the deficient type 1 immune responses of TLR2(-/-) mice are rescued upon s.c. injection of exogenous kininogens, along with trypomastigotes, supports the notion that generation of kinin "danger" signals is intensified through cooperative activation of TLR2 and B(2)R. In summary, we have described a s.c. infection model where type 1 immunity is vigorously up-regulated by bradykinin, an innate signal whose levels in peripheral tissues are controlled by an intricate interplay of TLR2, B(2)R, and ACE.
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PMID:Cooperative activation of TLR2 and bradykinin B2 receptor is required for induction of type 1 immunity in a mouse model of subcutaneous infection by Trypanosoma cruzi. 1705 63

Chagas heart disease (CHD), caused by Trypanosoma cruzi infection, is a significant cause of morbidity and mortality in South and Central America. Enalapril, an angiotensin converting enzyme (ACE) inhibitor, is an important drug used to ameliorate heart functional capacity and its remodelling in individuals presenting CHD. In this study, we evaluated the effects of enalapril on systemic and cardiac immune response during experimental acute CHD. C57BL/6 mice infected with 50 trypomastigote forms of T. cruzi (Colombian strain) were treated daily with enalapril (25 mg/kg) and, after 30 days, a reduction in seric levels of IFN-gamma, TNF-alpha, CCL5/RANTES and nitric oxide, but not in that of IL-10, was detected. This imbalance of cytokines reflects in a reduction of heart mononuclear infiltration and in an increasing of cardiac mast cells. Enalapril also presents a new and interesting in vitro and in vivo anti-T. cruzi activity probably acting on parasite oxidative pathway via cytochrome-P450. Our data show that enalapril exerts an important anti-T. cruzi and anti-inflammatory activity during acute CHD reducing inflammatory cells and, possibly, preventing fibrotic process in the chronic phase. Nevertheless, further studies are still necessary to clarify the mechanisms by which this drug is acting on the parasites and on the immune pathways.
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PMID:Enalapril prevents cardiac immune-mediated damage and exerts anti-Trypanosoma cruzi activity during acute phase of experimental Chagas disease. 2039 83