Current drug targets. Inflammation and allergy最新文献_第5页

Resident kidney cells and their involvement in glomerulonephritis. 常驻肾细胞及其在肾小球肾炎中的作用。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022132

Jennifer R Timoshanko, Peter G Tipping

{"title":"Resident kidney cells and their involvement in glomerulonephritis.","authors":"Jennifer R Timoshanko, Peter G Tipping","doi":"10.2174/1568010054022132","DOIUrl":"https://doi.org/10.2174/1568010054022132","url":null,"abstract":"Each year, worldwide, there is an increasing number of patients with chronic kidney disease that progress to end-stage renal disease. Glomerulonephritis (GN) is the commonest single cause of end-stage renal failure in the world. GN can be a manifestation of primary renal injury or may be a secondary feature of a systemic disease process, for example Systemic Lupus Erythematosus (SLE) and Anti-Neutrophilic Cytoplasmic Antibody (ANCA) associated vasculitis. Understanding of the immunopathogenesis of GN has advanced considerably over the last 25 years, particularly the immune system's role. The injurious role of infiltrating leukocytes and humoral mediators has been emphasised, however, the contribution of intrinsic renal cells has proved difficult to define. Most evidence for the pro-inflammatory capacity of intrinsic renal cells has been derived from in vitro studies. Although cytokine production by intrinsic renal cells has been demonstrated by immunohistochemistry and in situ hybridisation studies in renal tissue during the development of GN, the functional contribution of this cytokine production to renal injury was unknown. Little was known about direct and specific interactions between different glomerular cell types and infiltrating leukocytes in the pathogenesis of GN. The development of mice with genetic deficiencies of pro-inflammatory mediators and cytokines, and the technique of bone marrow transplantation into irradiated recipients to produce chimeric mice with restricted cytokine expression has allowed in vivo assessment of the functional contribution made by intrinsic renal cells. Studies have demonstrated the significant contribution of intrinsic renal cell derived cytokines (e.g. TNF) in mediating GN, whereas others (IL-1beta) have a relatively minor role.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 3","pages":"353-62"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010054022132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24958679","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: 17

Macrophages in inflammation. 炎症中的巨噬细胞。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022024

Nagatoshi Fujiwara, Kazuo Kobayashi

{"title":"Macrophages in inflammation.","authors":"Nagatoshi Fujiwara, Kazuo Kobayashi","doi":"10.2174/1568010054022024","DOIUrl":"https://doi.org/10.2174/1568010054022024","url":null,"abstract":"The inflammatory process is usually tightly regulated, involving both signals that initiate and maintain inflammation and signals that shut the process down. An imbalance between the two signals leaves inflammation unchecked, resulting in cellular and tissue damage. Macrophages are a major component of the mononuclear phagocyte system that consists of closely related cells of bone marrow origin, including blood monocytes, and tissue macrophages. From the blood, monocytes migrate into various tissues and transform macrophages. In inflammation, macrophages have three major function; antigen presentation, phagocytosis, and immunomodulation through production of various cytokines and growth factors. Macrophages play a critical role in the initiation, maintenance, and resolution of inflammation. They are activated and deactivated in the inflammatory process. Activation signals include cytokines (interferon gamma, granulocyte-monocyte colony stimulating factor, and tumor necrosis factor alpha), bacterial lipopolysaccharide, extracellular matrix proteins, and other chemical mediators. Inhibition of inflammation by removal or deactivation of mediators and inflammatory effector cells permits the host to repair damages tissues. Activated macrophages are deactivated by anti-inflammatory cytokines (interleukin 10 and transforming growth factor beta) and cytokine antagonists that are mainly produced by macrophages. Macrophages participate in the autoregulatory loop in the inflammatory process. Because macrophages produce a wide range of biologically active molecules participated in both beneficial and detrimental outcomes in inflammation, therapeutic interventions targeted macrophages and their products may open new avenues for controlling inflammatory diseases.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 3","pages":"281-6"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010054022024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24958193","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: 1197

Therapeutic targets of misguided T cells in systemic lupus erythematosus. 误导T细胞治疗系统性红斑狼疮的靶点。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022060

Tsutomu Takeuchi, Kensei Tsuzaka, Hideto Kameda, Kouichi Amano

{"title":"Therapeutic targets of misguided T cells in systemic lupus erythematosus.","authors":"Tsutomu Takeuchi, Kensei Tsuzaka, Hideto Kameda, Kouichi Amano","doi":"10.2174/1568010054022060","DOIUrl":"https://doi.org/10.2174/1568010054022060","url":null,"abstract":"It is widely accepted that T cells with defective function play a central role in the pathogenesis of systemic lupus erythematosus (SLE). The detailed molecular mechanism underlying the aberrant function of SLE T cells is now being revealed. The TCR zeta chain, transcription factor, elf-1, inflammation signal transducer NF-kB, and PKC theta have been identified as the responsible molecules. In contrast to the defective signal transduction molecules, surface structures such as adhesion molecules, and co-stimulators have been reported to increase in their expression and function. Glucocorticoids and immunosuppressive agents have greatly improved the outcome of acute diseases and 5-year survival rate. However, it is suggested that long-term survival and quality of life appears to be unsatisfactory. Although the medical management of SLE is not sufficient to warrant long-term survival of young patients, recent progress in anti-cytokine biologics therapy against rheumatoid arthritis (RA) has facilitated searching for the molecular targets of SLE. In this report, we briefly review the molecular basis of SLE pathogenesis, and discuss possible therapeutic targets in this disease, focusing particularly on signal transduction and adhesion molecules in T cells.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 3","pages":"295-8"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010054022060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24958195","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: 6

Chemokines and their receptors in chronic pulmonary disease. 慢性肺部疾病中的趋化因子及其受体。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022088

Nicholas W Lukacs, Cory M Hogaboam, Steven L Kunkel

{"title":"Chemokines and their receptors in chronic pulmonary disease.","authors":"Nicholas W Lukacs, Cory M Hogaboam, Steven L Kunkel","doi":"10.2174/1568010054022088","DOIUrl":"https://doi.org/10.2174/1568010054022088","url":null,"abstract":"The incidence of asthma has continued to rise worldwide with the number of severe asthmatic episodes dramatically increasing especially in children. Over the past several years researchers have realized that by controlling the influx of inflammatory cells that damage the airway and perpetuate the chronic responses, asthmatic disease can be attenuated. The modulation of the immune/inflammatory response has been primarily managed by use of inhaled and/or oral steroids. However, more specific therapy focused on inflammatory cell influx is desired to target the appropriate cell populations and alleviate specific aspects of disease without non-specific side effects. The chemokine family of cytokines control recruitment of leukocyte populations through specific receptors that are differentially expressed by certain cellular populations in various immune environments. Defining the type of receptors that are displayed by key cell populations involved in asthmatic responses has been the focus of many academic and pharmaceutic programs. This review will highlight the various areas that have been identified and those that appear to provide a future for therapeutic intervention.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 3","pages":"313-7"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010054022088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24958198","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: 38

Neutrophil-derived cytokines: potential therapeutic targets in inflammation. 中性粒细胞衍生的细胞因子:炎症的潜在治疗靶点。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022114

Tsuyoshi Kasama, Yusuke Miwa, Takeo Isozaki, Tsuyoshi Odai, Mitsuru Adachi, Steven L Kunkel

{"title":"Neutrophil-derived cytokines: potential therapeutic targets in inflammation.","authors":"Tsuyoshi Kasama, Yusuke Miwa, Takeo Isozaki, Tsuyoshi Odai, Mitsuru Adachi, Steven L Kunkel","doi":"10.2174/1568010054022114","DOIUrl":"https://doi.org/10.2174/1568010054022114","url":null,"abstract":"Polymorphonuclear neutrophils (PMNs) are usually thought of as the leukocyte population involved in acute inflammatory responses, acting as a first line of defense against invading microorganisms. These terminally differentiated cells are generally not thought of as an important source of de novo synthesis of polypeptide mediators. Recent progress has shown, however, that PMNs are able to synthesize cytokines in response to a variety of inflammatory stimuli and during certain pathological conditions. The expression profiles of PMN-derived cytokines are similar with those of monocytes/macrophages, major professional phagocytes. Like monocytes, PMNs are able to secrete proinflammatory cytokines [e.g., tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta], both CC and CXC chemokines [e.g., IL-8, interferon-inducible protein 10 (IP-10) and macrophage inflammatory protein (MIP)-1alpha], and angiogenic factors [e.g., vascular endothelial growth factor (VEGF)]. The secretion of cytokines by activated PMNs is regulated by immunoregulatory cytokines such as interferon (IFN)-gamma, IL-4, IL-10 and IL-13. In addition to acute inflammatory responses, PMNs and PMN-derived cytokines appear to be involved in the pathogenesis of such chronic inflammatory disorders as rheumatoid arthritis, inflammatory bowel diseases and mycobacterial infections. Conceivably, these findings place PMNs at a pivotal position where they regulate and orchestrate not only acute inflammatory responses but also chronic inflammation and immune regulation. As such, inhibition of PMN-derived cytokines is viewed as a potentially useful strategy for therapeutic immunointervention.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 3","pages":"273-9"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010054022114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25249349","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: 293

Pro and antiinflammatory properties of toxins from animal venoms. 动物毒液毒素的促炎和抗炎特性。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022150

Sandra H P Farsky, Edson Antunes, Suzana B V Mello

引用次数: 29

Pathways of T cell activation and terminal differentiation in chronic inflammation. 慢性炎症中T细胞活化和终末分化的途径。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022042

Pia Isomäki, Joanna M Clark, Manvinder Panesar, Andrew P Cope

{"title":"Pathways of T cell activation and terminal differentiation in chronic inflammation.","authors":"Pia Isomäki, Joanna M Clark, Manvinder Panesar, Andrew P Cope","doi":"10.2174/1568010054022042","DOIUrl":"https://doi.org/10.2174/1568010054022042","url":null,"abstract":"Immune and inflammatory responses are governed by antigen-specific T cells, whose activation, differentiation and effector function are induced by signals delivered via the T cell antigen receptor (TCR) and by costimulatory and cytokine receptors. The molecular events leading to the activation of naïve T cells have been extensively studied and are well characterized. Much less is known about the molecular and biochemical events regulating the activation of T cells in chronic inflammatory diseases such as rheumatoid arthritis (RA). This review examines the current state of knowledge of T cell activation in chronic inflammation, focusing on RA, and summarizes experimental data which indicate that the chronic inflammatory process may profoundly affect TCR and cytokine signal transduction pathways. We present evidence suggesting that in chronic inflammation, the antigen-driven TCR-mediated processes are attenuated, while cytokine-driven effector responses are sustained or even enhanced. The possible implications of this inbalance are discussed.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 3","pages":"287-93"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010054022042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24958194","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: 17

Bronchial epithelial cells in allergic reactions. 支气管上皮细胞的过敏反应。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022123

Hajime Takizawa

{"title":"Bronchial epithelial cells in allergic reactions.","authors":"Hajime Takizawa","doi":"10.2174/1568010054022123","DOIUrl":"https://doi.org/10.2174/1568010054022123","url":null,"abstract":"Bronchial epithelial cells (BEC) are known to play an integral role in the airway defense mechanism via mucociliary system as well as mechanical barriers. Recent studies further indicate that BEC produce and release biologically active compounds including lipid mediators, growth factors, endothelin and a variety of cytokines/chemokines important in the pathogenesis of airway disorders. Cytokines and chemokines produced by BEC include IL-6, IL-8, G-CSF, GM-CSF, RANTES, eotaxin and TARC. Pro-inflammatory cytokines IL-1 and TNF-alpha, generally upregulate expression and release these cytokines/chemokines. BEC from patients with bronchial asthma showed increased levels of mRNA for these potent inflammatory peptides. BEC also interact with immune and inflammatory cells by direct adhesion as well as by humoral factors including cytokines. For example, eosinophil adhesion to BEC may be an important signal for the activation and degranulation of eosinophils. BEC is also believed to take part in the airway mucosal immunity via Toll-like receptors. Finally, BEC may play a crucial role in the processes of airway remodeling by cross-talk with mesenchymal cells. These findings strongly suggest that BEC are actively involved as regulators of allergic inflammatory responses, and become a target for therapeutic intervention.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 3","pages":"305-11"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010054022123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24958197","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: 58

Endothelial cells in inflammation and angiogenesis. 炎症和血管生成中的内皮细胞。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022187

Zoltán Szekanecz, Alisa E Koch

{"title":"Endothelial cells in inflammation and angiogenesis.","authors":"Zoltán Szekanecz, Alisa E Koch","doi":"10.2174/1568010054022187","DOIUrl":"https://doi.org/10.2174/1568010054022187","url":null,"abstract":"Endothelial cells are involved in leukocyte extravasation underlying inflammation. A number of adhesion molecules play a role in leukocyte-endothelial interactions. New vessel formation, termed angiogenesis, is also crucial for leukocyte extravasation. The outcome of neovascularization is highly dependent on the balance or imbalance between angiogenic mediators and inhibitors. There have been several attempts to therapeutically interfere with the cellular and molecular mechanisms, such as leukocyte-endothelial cell adhesion and angiogenesis. Most studies have been performed using animal models of various types of inflammation, such as arthritis. In addition, a very limited number of human clinical trials gave promising results. In this review, authors summarize the most relevant information on adhesion molecules, as well as angiogenic and angiostatic agents. In addition, further perspectives of anti-adhesive and anti-angiogenic therapy are also discussed. Specific targeting of pathological endothelial function including adhesion and angiogenesis, may be useful for the future management of various inflammatory diseases.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 3","pages":"319-23"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010054022187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24958199","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: 33

Osteoblasts and osteoclasts in bone remodeling and inflammation. 成骨细胞和破骨细胞在骨重塑和炎症中的作用。

Current drug targets. Inflammation and allergy Pub Date : 2005-06-01 DOI: 10.2174/1568010054022015

Yoshiya Tanaka, Shingo Nakayamada, Yosuke Okada

{"title":"Osteoblasts and osteoclasts in bone remodeling and inflammation.","authors":"Yoshiya Tanaka, Shingo Nakayamada, Yosuke Okada","doi":"10.2174/1568010054022015","DOIUrl":"https://doi.org/10.2174/1568010054022015","url":null,"abstract":"Bone homeostasis is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Osteoblasts not only play a central role in bone formation by synthesizing multiple bone matrix proteins, but regulate osteoclast maturation by soluble factors and cognate interaction, resulting in bone resorption. Osteoclast maturation requires stimulation by RANKL expressed on osteoblasts, and the cognate interaction is mediated by firm adhesion via ICAM-1. During the processes, pro-inflammatory cytokines such as IL-1 and TNF-alpha, cause an imbalance in bone metabolism, by favoring bone resorption via the induction of RANKL and ICAM-1 on osteoblasts. These inflammatory signals originate from the immune system, the largest source of cell-derived regulatory signals, and such immunological signals to the bone are transmitted primarily via osteoblasts to induce osteoclast maturation, resulting in secondary osteoporosis. Actually, such phenomena mainly occur at the interface between proliferating synovium and bone tissue in rheumatoid arthritis (RA). Thus, therapeutic strategies for these conditions, an anti-TNF-alpha antibody and an IL-1 receptor antagonist, effective for treating RA disease activity, also reduce secondary osteoporosis and joint destruction. Based on an improved understanding of immune signals, investigation of the suppression of cell functions may lead to improved understanding and better treatment of diseases of bone metabolism and osteoporosis.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"4 3","pages":"325-8"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010054022015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24958200","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: 344