Current drug targets. Inflammation and allergy最新文献_第6页

Mesangial cells and glomerular inflammation: from the pathogenesis to novel therapeutic approaches. 系膜细胞和肾小球炎症:从发病机制到新的治疗方法。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022169

Carmen Gómez-Guerrero, Purificación Hernández-Vargas, Oscar López-Franco, Guadalupe Ortiz-Muñoz, Jesús Egido

{"title":"Mesangial cells and glomerular inflammation: from the pathogenesis to novel therapeutic approaches.","authors":"Carmen Gómez-Guerrero, Purificación Hernández-Vargas, Oscar López-Franco, Guadalupe Ortiz-Muñoz, Jesús Egido","doi":"10.2174/1568010054022169","DOIUrl":"https://doi.org/10.2174/1568010054022169","url":null,"abstract":"The mesangium occupies a central anatomical position in the glomerulus, and also plays an important regulatory role in immune-mediated glomerular diseases, with an active participation in the response to local inflammation. In general, the mesangial cell responses to the pathological stimuli are associated with the main events of glomerular injury: leukocyte infiltration, cell proliferation and fibrosis. Leukocyte migration and infiltration into the glomerulus is responsible for the initiation and amplification of glomerular injury, and is mediated by adhesion molecules and chemokines, which can be locally synthesized by mesangial cells. The increase in mesangial cell number is also due to proliferation of intrinsic mesangial cell population. Regulatory mechanisms of mesangial cell replication include a complex array of factors which control cell proliferation, survival and apoptosis. Mesangial matrix accumulation leading to glomerulosclerosis, is a consequence of an imbalance between matrix production and degradation, and is controlled by growth factors and pro-inflammatory cytokines. The initial phase of immune-mediated glomerular inflammation depends on the interaction of immune complexes with specific Fc receptors in infiltrating leukocytes and resident mesangial cells, the ability of immune complexes to activate complement system, and on local inflammatory processes. Activated mesangial cells then produce many inflammatory mediators leading to amplification of the injury. This review will focus on the biological functions of mesangial cells that contribute to glomerular injury, with special attention to immune-mediated glomerulonephritis. Furthermore, new therapies based on the pathophysiology of the mesangial cell that are being developed in experimental models are also proposed.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 3","pages":"341-51"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010054022169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24958678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 71

Chemokines and brain functions. 趋化因子和脑功能。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022097

Ghazal Banisadr, William Rostène, Patrick Kitabgi, Stéphane Mélik Parsadaniantz

{"title":"Chemokines and brain functions.","authors":"Ghazal Banisadr, William Rostène, Patrick Kitabgi, Stéphane Mélik Parsadaniantz","doi":"10.2174/1568010054022097","DOIUrl":"https://doi.org/10.2174/1568010054022097","url":null,"abstract":"Chemokines are small secreted proteins that chemoattract and activate immune and non-immune cells both in vivo and in vitro. Besides their well-established role in the immune system, several recent reports have suggested that chemokines and their receptors may also play a role in the central nervous system (CNS). The best-known central action is their ability to act as immuno-inflammatory mediators. Indeed, these proteins regulate the leukocyte infiltration in the brain during inflammatory and infectious diseases. However, recent studies clearly demonstrate that chemokines and their receptors are constitutively expressed by glial and neuronal cells in the CNS, where they are involved in intercellular communication. The goal of this review is to summarize recent information concerning the role of chemokines in brain functions. The first part will focus on the expression of chemokines and their receptors in the CNS with the main spotlight on the neuronal expression. In the second part, we will discuss the role of chemokines and their receptors in normal brain physiology. Because several chemokines are involved in neuroinflammatory and neurodegenerative disorders, the role of chemokines and their receptors in these diseases is reviewed further in this section. In conclusion, the implication of chemokines in cellular communication could allow: i) to identify a new pathway for neuron-neuron and/or glia-glia and/or neuron-glia communications that are relevant to both normal brain function and neuroinflammatory and neurodegenerative diseases; ii) to develop new therapeutic approaches for still untreatable diseases further.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 3","pages":"387-99"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010054022097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24958682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 89

Editorial [Hot Topic: The Kinetics and Profiles of Inflammatory Cells During Inflammatory and Allergic Responses (Guest Editor: Tsuyoshi Kasama)] 社论[热门话题:炎症和过敏反应过程中炎症细胞的动力学和特征(特邀编辑:Kasama Tsuyoshi)]

Current drug targets. Inflammation and allergy Pub Date : 2005-05-31 DOI: 10.2174/1568010054022105

T. Kasama

引用次数: 1

The role of beta(2)-adrenergic receptors in inflammation and allergy. β(2)-肾上腺素能受体在炎症和过敏中的作用

Current drug targets. Inflammation and allergy Pub Date : 2005-04-01 DOI: 10.2174/1568010053586309

Brigita Sitkauskiene, Raimundas Sakalauskas

{"title":"The role of beta(2)-adrenergic receptors in inflammation and allergy.","authors":"Brigita Sitkauskiene, Raimundas Sakalauskas","doi":"10.2174/1568010053586309","DOIUrl":"https://doi.org/10.2174/1568010053586309","url":null,"abstract":"Essential role of beta(2)-adrenoreceptor (beta(2)AR) in airway relaxation is well established. Nevertheless, beta(2)AR seems playing an actual role in allergy and inflammation. Interaction between beta(2)AR and proinflamatory cytokines in airway smooth muscle has been revealed. Being located on proinflamatory cells, beta(2)ARs may influence function of these cells in vivo. It was clear established, that stimulation of beta(2)AR inhibits release of proinflamatory mediators from mast cells, influences T-cell growth and function, eosinophil survival and function, including GM-CSF- or PAF-induced degranulation. Stimulation of beta(2)ARs, located on alveolar macrophages and epithelial cells, has ambiguity influence on their regulation and function, including phagocytosis and mediator secretion, in vivo. Vascular responses, resulting in inhibition of plasma exudation were confirmed, but modulation of sensory nerves via beta(2)AR is not certain yet. beta(2)AR-agonists are effective in treatment of immediate allergic reactions, but desensitisation of beta(2)ARs on inflammatory cells may result in paradoxical effects, especially in asthma. In summary, it is clear that beta(2)ARs may play an anti-inflammatory role in vitro. Unfortunately, in vitro data have shown limited applicability in vivo; therefore further research in this field is required.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 2","pages":"157-62"},"PeriodicalIF":0.0,"publicationDate":"2005-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010053586309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25078218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 21

Evidence that pregnancy specific glycoproteins regulate T-Cell function and inflammatory autoimmune disease during pregnancy. 妊娠期特异性糖蛋白调节t细胞功能和炎症性自身免疫性疾病的证据

Current drug targets. Inflammation and allergy Pub Date : 2005-04-01 DOI: 10.2174/1568010053586255

Bruce F Bebo, Gabriela S Dveksler

{"title":"Evidence that pregnancy specific glycoproteins regulate T-Cell function and inflammatory autoimmune disease during pregnancy.","authors":"Bruce F Bebo, Gabriela S Dveksler","doi":"10.2174/1568010053586255","DOIUrl":"https://doi.org/10.2174/1568010053586255","url":null,"abstract":"The capacity of the pregnancy state to regulate T-cell function is well documented. A consequence of this regulation is that many T-cell mediated autoimmune disorders, including multiple sclerosis (MS) are suppressed during pregnancy. The suppression of MS during pregnancy is more potent than the currently available treatments for this disease. Thus, the study of immunoregulatory factors of pregnancy could potentially result in the discovery of novel MS treatments. The regulation of T-cell function during pregnancy is likely the result of significant hormonal changes and may well involve immunoregulatory proteins derived from the placenta. Pregnancy specific glycoproteins (PSGs) are the most abundant placentally derived glycoproteins in the maternal serum. The levels of PSGs are highest during the third trimester of pregnancy, a time marked by the most profound suppression of MS disease attacks. Recent studies by our laboratories, and others, suggest that PSGs regulate T-cell function. We propose this regulation occurs by two distinct, but complementary mechanisms. PSGs may regulate T-cell function by (1) directly signaling tetraspanins present on the cell surface and by (2) regulating T-cell function indirectly through signaling of tetraspanins expressed by macrophages and dendritic cells. In this report, we will review evidence implicating PSGs as important immunoregulatory proteins and discuss our recent findings regarding the mechanisms by which PSGs regulate T-cell function.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 2","pages":"231-7"},"PeriodicalIF":0.0,"publicationDate":"2005-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010053586255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25077001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 31

Modulation of TNF receptor family members to inhibit autoimmune disease. 调节TNF受体家族成员抑制自身免疫性疾病。

Current drug targets. Inflammation and allergy Pub Date : 2005-04-01 DOI: 10.2174/1568010053586345

Andrew D Weinberg, Ryan Montler

引用次数: 13

Arachidonic acid signaling in pathogenesis of allergy: therapeutic implications. 花生四烯酸信号在过敏发病机制中的作用:治疗意义。

Current drug targets. Inflammation and allergy Pub Date : 2005-04-01 DOI: 10.2174/1568010053586354

Anna Serrano-Mollar, Daniel Closa

{"title":"Arachidonic acid signaling in pathogenesis of allergy: therapeutic implications.","authors":"Anna Serrano-Mollar, Daniel Closa","doi":"10.2174/1568010053586354","DOIUrl":"https://doi.org/10.2174/1568010053586354","url":null,"abstract":"In recent years, significant progress has been made in understanding the involvement of pro-inflammatory lipidic mediators in the pathogenesis of allergic diseases. The most relevant lipidic mediator is arachidonic acid and its metabolites. Arachidonic acid is the precursor for biosynthesis of eicosanoids, potent mediators of inflammation that have been implicated in the pathogenesis of diverse disease processes. Eicosanoids are mainly synthesized by the action of cyclo-oxygenase (prostaglandin endoperoxide synthase) that generates prostaglandins and thromboxane, and 5-lipoxygenase, which leads to the production of leukotrienes. In addition, 12- and 15-lipoxygenase are found in mammalian systems. The activity of these enzymes results in the formation of different hydroxyeicosatetraenoic acids, but their functions in vivo have not been clearly established in normal or pathological states. Since several arachidonic acid metabolites clearly play an important role in allergic response, a substantial effort has been directed to understanding the cellular and molecular aspects of these pathways and their pharmacological modulation. This review summarizes some of these aspects based on our current knowledge of the involvement of arachidonic metabolism in the pathogenesis of allergic diseases and outlines the potential therapeutic opportunities that can result from the modulation of these metabolites.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 2","pages":"151-5"},"PeriodicalIF":0.0,"publicationDate":"2005-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010053586354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25078217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Targeting chemoattractant receptors in allergic inflammation. 过敏性炎症中的靶向化学引诱剂受体。

Current drug targets. Inflammation and allergy Pub Date : 2005-04-01 DOI: 10.2174/1568010053586318

Daniele D'Ambrosio

{"title":"Targeting chemoattractant receptors in allergic inflammation.","authors":"Daniele D'Ambrosio","doi":"10.2174/1568010053586318","DOIUrl":"https://doi.org/10.2174/1568010053586318","url":null,"abstract":"Asthma, atopic dermatitis, allergic rhinitis, which are amongst the most clinically relevant allergic disorders in industrialized countries affecting hundreds of millions of people world-wide, are characterized by tissue infiltration of Th2 cells, eosinophils, mast cells and basophils. Recruitment of these leukocyte subpopulations proceeds in response to specific chemotactic clues produced by tissue resident cells and is further amplified by incoming leukocytes. Over the last decade a number of receptors for chemokines and other chemoattractants have been identified on distinct leukocyte subpopulations participating to the pathogenesis of allergic inflammation. Preferential expression of discrete chemoattractant receptors on relevant cell types and their up-regulation in affected organs and animal models of allergic inflammation has helped to restrict the list of culprits. Although searching of the appropriate target for pharmacological intervention is still in progress, discrete chemoattractant receptors are already attracting a strong interest from the pharmaceutical industry. Here, we will review the most recent advances on the role that specific chemoattractant receptors play in the pathogenesis of allergic inflammation and will discuss emerging developments in this field.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 2","pages":"163-7"},"PeriodicalIF":0.0,"publicationDate":"2005-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010053586318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25078219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Inflammatory mediators as potential therapeutic targets in the spine. 炎症介质作为脊柱的潜在治疗靶点。

Current drug targets. Inflammation and allergy Pub Date : 2005-04-01 DOI: 10.2174/1568010053586372

Sally Roberts, Robin C Butler

{"title":"Inflammatory mediators as potential therapeutic targets in the spine.","authors":"Sally Roberts, Robin C Butler","doi":"10.2174/1568010053586372","DOIUrl":"https://doi.org/10.2174/1568010053586372","url":null,"abstract":"Inflammation plays a variable part in the pathogenesis of several spinal disorders. Ankylosing spondylitis is a chronic inflammatory arthropathy of the spine and rheumatoid arthritis, whilst affecting predominantly limb joints, also affects the cervical spine in a significant proportion of people. Inflammation is also involved in disorders such as disc herniation and sciatica, which have previously been thought of as being primarily mechanical or degenerative. Anti-inflammatory agents which have been shown to be effective elsewhere in the body are discussed in this review as possible therapeutic agents in the spine. As the inflammatory cascade and immunopathology of these conditions continue to be elucidated, it has become apparent that individual molecules may be potential targets for inactivation or down-regulation. Candidates include pro-inflammatory cytokines, such as TNF-alpha, cytokines, e.g. IL-1 and IL-15, or enzymes enhancing the inflammation pathway such as the cyclooxygenases. Hence treatments based on inactivation of these molecules by various mechanisms, including antibodies, receptor antagonists, enzyme inhibitors or gene therapy, are being introduced. However, the mode of action of a particular molecule can be complex and sometimes apparently contradictory. For example, TNF-alpha is known to play an important role in promoting inflammation by upregulating expression of cell adhesion molecules on endothelial cells and stimulating the production of reactive oxygen intermediates, nitric oxide and prostaglandins. However, it can also have an immunosuppressive and anti-inflammatory role after prolonged release. Therefore, although inhibitors of many of these molecules are now in clinical application and trials (many with promising results in rheumatoid arthritis), it is important to remain vigilant and monitor long-term outcomes particularly when these treatments are used in clinical syndromes with relatively poorly defined immunopathology such as spinal disorders.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 2","pages":"257-66"},"PeriodicalIF":0.0,"publicationDate":"2005-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010053586372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25077543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

Matrix metalloproteinase-9 and airway remodeling in asthma. 基质金属蛋白酶-9与哮喘气道重塑。

Current drug targets. Inflammation and allergy Pub Date : 2005-04-01 DOI: 10.2174/1568010053586246

Hiroyuki Ohbayashi, Kaoru Shimokata

{"title":"Matrix metalloproteinase-9 and airway remodeling in asthma.","authors":"Hiroyuki Ohbayashi, Kaoru Shimokata","doi":"10.2174/1568010053586246","DOIUrl":"https://doi.org/10.2174/1568010053586246","url":null,"abstract":"Airway remodeling is a major change responsible for irreversible asthmatic airflow restriction. The Th-2 cytokines-dominant eosinophilic inflammatory mechanism cannot fully explain the progressive subepithelial fibrosis and structural changes in the extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are the key enzymes responsible for ECM degradation. MMPs are normally produced and secreted under the tight regulation of, at least, 3 different levels: the gene transcriptional level, the activation of the latent form of enzyme, and the inactivation by specific endogenous inhibitors. In asthmatic condition, as shown by the large amount of accumulated evidence in this review, MMP-9 is the most relevant among the 23 kinds of human MMPs at present detected. Although the mechanism is still under investigation and not accurately known, the imbalance between MMP-9 and tissue inhibitor of metalloproteinase-1 is considered a major theory to explain the progression of asthmatic airway remodeling. Various inflammatory cytokines including TGF beta and growth factors play a pivotal role in MMP-9 production and secretion. This review mainly focuses upon the pivotal role of MMP-9 in airway remodeling, and also upon major cellular source of MMP-9 in asthma such as eosinophils, neutrophils, epithelial cells and alveolar macrophages. This review also refers to the partial contribution of nitric oxide to MMP-9 in asthma.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 2","pages":"177-81"},"PeriodicalIF":0.0,"publicationDate":"2005-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010053586246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25076996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 93