Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial cells, by virtue of their capacity to express adhesion molecules and cytokines, are intricately involved in inflammatory processes. Endothelial cells have been shown to express interleukin-1 (IL-1), IL-5, IL-6, IL-8, IL-11, IL-15, several colony-stimulating factors (CSF), granulocyte-CSF (G-CSF), macrophage CSF (M-CSF) and granulocyte-macrophage CSF (GM-CSF), and the chemokines, monocyte chemotactic protein-1 (MCP-1), RANTES, and growth-related oncogene protein-alpha (GRO-alpha). IL-1 and tumor necrosis factor-alpha (TNF-alpha) produced by infiltrating inflammatory cells can induce endothelial cells to express several of these cytokines as well as adhesion molecules. Induction of these cytokines in endothelial cells has been demonstrated by such diverse processes as hypoxia and bacterial infection. Recent studies have demonstrated that adhesive interactions between endothelial cells and recruited inflammatory cells can also signal the secretion of inflammatory cytokines. This cross-talk between inflammatory cells and the endothelium may be critical to the development of chronic inflammatory states. Endothelial-derived cytokines may be involved in hematopoiesis, cellular chemotaxis and recruitment, bone resorption, coagulation, and the acute-phase protein synthesis. As many of these processes are critical to the maturation of an inflammatory and reparative state, it appears likely that endothelial-derived cytokines play a crucial role in several diseases, including atherosclerosis, graft rejection, asthma, vasculitis, and sepsis. Genetic and pharmacologic manipulation of endothelial-derived cytokines provides an additional approach to the management of chronic inflammatory diseases.
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PMID:Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease. 1009 Mar 94

The Fus1 gene resides in the critical 3p21.3 human chromosomal region deleted in lung and breast cancers. Recently, the tumour suppressor properties of Fus1 were confirmed experimentally by intra-tumoural administration of Fus1 that suppressed experimental lung metastasis in mice. We generated Fus1-deficient mice that were viable, fertile, and demonstrated a complex immunological phenotype. Animals with a disrupted Fus1 gene developed signs of autoimmune disease, such as vasculitis, glomerulonephritis, anaemia, circulating autoantibodies, and showed an increased frequency of spontaneous vascular tumours. Preliminary analysis of immune cell populations revealed a consistent defect in NK cell maturation in Fus1 null mice that correlated with changes in the expression of IL-15. Injection of IL-15 into Fus1 knockout mice completely rescued the NK cell maturation defect. Based on these results, we propose the hypothesis that Fus1 deficiency affects NK cell maturation through the reduction of IL-15 production but does not directly alter their developmental capacity. Since acquired immunity was not affected in Fus1-deficient animals, we suggest a relationship between the Fus1 protein and the regulation of innate immunity via IL-15 production. The increased frequency of spontaneous cancers and the development of an autoimmune syndrome in Fus1 null mice imply that these mice could serve as a model for studying molecular mechanisms of anti-tumour immunity and autoimmunity.
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PMID:Autoimmunity, spontaneous tumourigenesis, and IL-15 insufficiency in mice with a targeted disruption of the tumour suppressor gene Fus1. 1731 11

Improved knowledge regarding the pathogenetic mechanisms involved in autoimmune diseases has contributed to the development of biological therapies, with advances in cytokine research in particular revolutionizing the treatment of several autoimmune diseases. Anti-TNF agents are the most promising drugs for reducing symptoms, slowing or arresting joint damage, and preventing functional disability in patients with rheumatoid arthritis who fail to respond to standard disease-modifying antirheumatic drugs. Anti-TNF agents may also be useful in the treatment of other rare disorders, such as various forms of vasculitis, polymyositis and dermatomyositis. However, clinical trials of TNF inhibitors and inhibitors of the proinflammatory cytokines IL-1, IL-6, IL-12, IL-15, IL-17 and IL-23 demonstrated that the activity of such compounds is accompanied by a series of adverse events that needs to be addressed. This review describes the efficacy and adverse events associated with anti-cytokine treatments for autoimmune rheumatic diseases.
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PMID:Anti-cytokine antibodies for rheumatic diseases. 1987 88

Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) comprise the most common group of primary systemic vasculitides and include Wegener;s granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS), and renal-limited vasculitis (RLV). AAV share the feature of necrotizing predominantly small vessel vasculitis, but are otherwise distinct diseases with differences in the genetic background, epidemiological and exogenous factors, immune and pathologic features, preferences of organ involvement, and frequencies of ANCA-association. MPA and RLV display solely vasculitic features, whereas WG and CSS are characterized by both granulomatous disease and a systemic vasculitis. Chronic inflammation and neoformation of tertiary lymphoid tissue appear to initiate and maintain the break of tolerance and induction of ANCA in AAV. A number of mechanisms are implied in this process, e.g., nasal S. aureus carriage suggestive of a potential link to infection in WG, danger-signals, neutrophil extracellular traps (NETs), the protease-activated receptor (PAR)-2, cytokines (Th1/Th2-type, IL-15, IL-17), and NK-like T-cells. The outcome of AAV has greatly improved since the introduction of immunosuppressive therapy. Still, the prognosis is impaired by high relapse rates and side effects of immunosuppressive therapy. Biologicals emerged as a new class of drugs that may help to improve outcome and reduce side effects of conventional treatments. So far, anti-CD20 therapy (rituximab) and TNF-alpha-antagonists represent strategies for refractory disease, but evidence from controlled trials is still lacking. Controlled trials for "routine" remission induction with these biological are also pending. New therapy principles hold further promise for the future.
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PMID:Update on clinical, pathophysiological and therapeutic aspects in ANCA-associated vasculitides. 2002 91