Current drug targets. Inflammation and allergy最新文献

{"title":"Interactions of sex steroids with mechanisms of inflammation.","authors":"Maik Obendorf,&nbsp;Vladimir K Patchev","doi":"10.2174/1568010042634460","DOIUrl":"https://doi.org/10.2174/1568010042634460","url":null,"abstract":"<p><p>Differential sex-specific liability to inflammatory and autoimmune diseases, and changes in symptom severity in association with physiological fluctuations in gonadal secretions are indicative of significant contribution of sex hormones to the regulation of immune responsiveness. Apart from a postulated role in sex-specific organization of the immune system during ontogeny, gonadal steroids may influence the immune response in numerous ways. This review analyzes existing concepts, experimental and clinical data, aiming at the definition of cellular and molecular mechanisms which may serve as suitable targets for discovery of immunomodulatory drugs whose principal feature is specific interaction with sex hormone receptors. Separation of immunomodulatory effects of sex steroids from those which are exerted by glucocorticoids, and subsequent identification of sex-hormone-specific molecular targets appear to be crucial for the justification of drug discovery on the basis of sex steroid receptor ligands.</p>","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"3 4","pages":"425-33"},"PeriodicalIF":0.0,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010042634460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24848297","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}

{"title":"The glucocorticoid receptor as target for classic and novel anti-inflammatory therapy.","authors":"Andrew C B Cato,&nbsp;Heike Schäcke,&nbsp;Wolfram Sterry,&nbsp;Khusru Asadullah","doi":"10.2174/1568010042634479","DOIUrl":"https://doi.org/10.2174/1568010042634479","url":null,"abstract":"Glucocorticoids are well known for their potent anti-inflammatory and immune-suppressive actions. Their clinical usefulness remains limited due to serious side effects that have necessitated a search for ways of improving their benefit-risk ratios. Mechanistically, glucocorticoids function by interacting with an intracellular receptor, the glucocorticoid receptor, a ligand-regulated transcription factor that positively or negatively alters the expression of specific genes. While it is well accepted that distinct negative regulatory action of this receptor forms the basis of the desired anti-inflammatory effects of glucocorticoids, not much is known about the function of the receptor that contributes to its side effects. The fact that a number of cellular metabolic control genes are positively regulated by glucocorticoids makes positive regulation of gene expression an attractive mode of action for the adverse effects. Positive regulation of gene expression by glucocorticoids, however, occurs through different mechanisms and in cell-type specific manner making it difficult to predict its possible biological effects in one single assay procedure. Recent advances in the molecular action of the receptor are gradually revealing different assays and important characteristics that can be put together in determining the physiological consequences of the different transactivation functions of the glucocorticoid receptor. These will provide invaluable source of information for the search of glucocorticoid receptor agonists with potent anti-inflammatory but reduced side effects.","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"3 4","pages":"347-53"},"PeriodicalIF":0.0,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010042634479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24848292","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}

{"title":"The lung in immune-mediated disorder: rheumatoid arthritis.","authors":"Antonio Castagnaro,&nbsp;Alfredo Chetta,&nbsp;Emilio Marangio,&nbsp;Maurizio Zompatori,&nbsp;Dario Olivieri","doi":"10.2174/1568010042634532","DOIUrl":"https://doi.org/10.2174/1568010042634532","url":null,"abstract":"<p><p>Various pleuro-pulmonary abnormalities are known to complicate vascular collagen diseases, particularly, rheumatoid arthritis. Each component of the respiratory system is affected, either separately or in combination. Although most pulmonary complications appear in an established case of collagen vascular disease, in certain conditions, the lung disease precedes the more typical manifestation. While some complications are asymptomatic and tend to be resolved spontaneously (for e.g. pleuritis and rheumatoid nodules), others may cause severe or fatal conditions (interstitial pneumonia and constrictive bronchiolitis). The incidence of interstitial lung disease is increasing in vascular collagen disease. This may be mainly attributed to the increase use of invasive techniques such as bronchoscopy and video-assisted thoracoscopic surgery and in part due to the use of high resolution computed tomography, and functional pulmonary tests.</p>","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"3 4","pages":"449-54"},"PeriodicalIF":0.0,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010042634532","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24848265","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}

{"title":"Pulmonary hypertension and systemic diseases.","authors":"Rossella Paolini,&nbsp;Michela Armigliato,&nbsp;Sergio Zamboni","doi":"10.2174/1568010042634613","DOIUrl":"https://doi.org/10.2174/1568010042634613","url":null,"abstract":"<p><p>Secondary pulmonary hypertension (sPH) may develop as a result of few systemic diseases as endocrine diseases, HIV infection, collagen diseases, liver and hematological disorders. In this review we discuss the role of systemic diseases in inducing PH starting from a pathological classification.</p>","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"3 4","pages":"459-67"},"PeriodicalIF":0.0,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010042634613","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24848267","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}

{"title":"Nuclear receptors: overview and classification.","authors":"Natalia Novac,&nbsp;Thorsten Heinzel","doi":"10.2174/1568010042634541","DOIUrl":"https://doi.org/10.2174/1568010042634541","url":null,"abstract":"<p><p>The nuclear receptor superfamily comprises a large group of transcription factors that play a key regulatory role in development and homeostasis of multicellular organisms. A special feature of nuclear receptors is their ability to bind to condensed chromatin templates, which makes them important initiators of gene transcription. Moreover, the ability of nuclear receptors to sequentially recruit a variety of transcription factors and coregulators to target promoters and to orchestrate the whole process of gene transcription confirms their biological significance and stimulates intensive research and a high level of scientific interest in this field. In this review, we summarise current knowledge regarding the structure and function of nuclear receptors as principal regulators of gene expression. Emphasis is given to the molecular mechanisms of nuclear receptor-mediated transcriptional activation and repression including recent progress made in this area.</p>","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"3 4","pages":"335-46"},"PeriodicalIF":0.0,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010042634541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24848291","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}

{"title":"Nur77 family of nuclear hormone receptors.","authors":"Hui-Chen Hsu,&nbsp;Tong Zhou,&nbsp;John D Mountz","doi":"10.2174/1568010042634523","DOIUrl":"https://doi.org/10.2174/1568010042634523","url":null,"abstract":"<p><p>Among the numerous steroidal and orphan nuclear receptors encoded within mammalian genomes, several are involved in the regulation of apoptosis. The authors review here recent studies on members of the Nur77 family of orphan receptors including Nur77, Nurr1 and Nor-1. These transcription factors were initially identified in nerve cells, but also play key roles in the development and the effector functions of T lymphocytes and other cells and tissues. Nur77 can also act as a modulator of transcription for other orphan steroid receptors. Regulation of the Nur77 orphan receptor family members are tightly associated with transcriptional co-factors including co-repressors and co-activators. Also, one interesting aspect of the Nur77 orphan receptor family members is that depending on its location in the mitochondria or nucleus, these orphan receptors exhibit differential roles in determining cell death or cell growth. Numerous studies demonstrated the importance of Nur77 subfamily members in regulations of early embryogenesis, thymocyte negative selection, gene expression in hypothalamic-pituitary adrenal axis, chronic inflammatory response, and vascular smooth muscle cell proliferation. This review intends to integrate the importance of nuclear receptors in health and disease, and as potential targets for drug discovery by comparing the difference and similarity in the biochemical mechanisms of action used by the classic steroid/endocrine receptors and the orphan receptors to lead to identification of novel targets in manipulating the transcriptional functions and physiologic pathways for the orphan nuclear receptors.</p>","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"3 4","pages":"413-23"},"PeriodicalIF":0.0,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010042634523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24848296","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}

{"title":"Pulmonary involvement in inflammatory bowel disease.","authors":"Maurizio Marvisi,&nbsp;Emanuele Bassi,&nbsp;Giuseppe Civardi","doi":"10.2174/1568010042634514","DOIUrl":"https://doi.org/10.2174/1568010042634514","url":null,"abstract":"<p><p>Inflammatory bowel disease is a systemic illness that may involve the lung. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. Bronchoalveolar lavage data show an increase percentage of neutrophils and steroids are very effective in the majority of cases. Some patients present severe tracheal inflammation and obstruction with an inflammatory mass bulging into the tracheal lumen. Others show a small airway involvement with or without bronchiolitis obliterans organizing pneumonia pattern and have an equivocal response to steroids. In recent years many investigators demonstrated latent pulmonary involvement with a reduction in lung transfer factor and a small airways disorders.</p>","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"3 4","pages":"437-9"},"PeriodicalIF":0.0,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010042634514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24848263","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}

{"title":"Recent advances in the mechanisms of action and physiological functions of the retinoid-related orphan receptors (RORs).","authors":"Anton M Jetten","doi":"10.2174/1568010042634497","DOIUrl":"https://doi.org/10.2174/1568010042634497","url":null,"abstract":"<p><p>Retinoid-related orphan receptors ROR alpha, -beta, and -gamma are evolutionarily related transcription factors belonging to the steroid hormone receptor superfamily. Studies of ROR mutant mice revealed that these receptors are critical in the regulation of a number of physiological processes. ROR alpha plays a key role in the development of the cerebellum particularly in the regulation of Purkinje cell differentiation and proliferation of granule cell progenitors. ROR alpha has also been implicated in the maintenance of bone tissue and mice deficient in ROR alpha exhibit a greater susceptibility to atherosclerosis. ROR gamma is essential for lymph node organogenesis and plays a key role in the generation or survival of lymphoid tissue inducer (Lti) cells. ROR gamma is also critical in thymopoiesis where it controls differentiation and promotes the survival of thymocytes by positively regulating Bcl-X(L) expression. Several studies have indicated a regulatory role for RORs in circadian behavior. In several tissues, the expression of RORs oscillates during circadian rhythm while mice deficient in ROR beta exhibit an altered circadian rhythm. ROR alpha and ROR gamma have been implicated in the control of various immune responses. Mice deficient in ROR gamma exhibit a reduced susceptibility to allergen-induced airway inflammation while ROR alpha null mice show a prolonged inflammatory response to lipopolysaccharide. Recent analyses of the crystal structure and transcriptional activity of RORs revealed that cholesterol and specific cholesterol derivatives behave as agonists of ROR alpha while certain retinoids function as partial antagonists of ROR beta and ROR gamma. These studies indicate that ROR activity and, as a consequence physiological processes regulated by RORs, can be modulated by exogenous (ant)agonists. Therefore, the discovery of new (ant)agonists may lead to the development of novel therapeutic strategies for human disease in which RORs have been implicated.</p>","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":"3 4","pages":"395-412"},"PeriodicalIF":0.0,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010042634497","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24848295","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}

{"title":"Retinoid receptors in inflammatory responses: a potential target for pharmacology.","authors":"Stéphane Kuenzli,&nbsp;Christian Tran,&nbsp;Jean-Hilaire Saurat","doi":"10.2174/1568010042634587","DOIUrl":"https://doi.org/10.2174/1568010042634587","url":null,"abstract":"","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":" ","pages":"355-60"},"PeriodicalIF":0.0,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010042634587","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25121725","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}

{"title":"Nuclear receptors: old targets, new opportunities.","authors":"Khusru Asadullah,&nbsp;Rainer Metternich","doi":"10.2174/1568010042634569","DOIUrl":"https://doi.org/10.2174/1568010042634569","url":null,"abstract":"","PeriodicalId":86954,"journal":{"name":"Current drug targets. Inflammation and allergy","volume":" ","pages":"333-4"},"PeriodicalIF":0.0,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568010042634569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24852328","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}