Pub Date : 2005-12-01DOI: 10.2174/156801405774933188
Can G Pham, Salvatore Papa, Concetta Bubici, Francesca Zazzeroni, Guido Franzoso
NF-κB/Rel transcription factors are well-known for their roles in the regulation of inflammation and immunity. NF-κB also blocks programmed cell death (PCD) or apoptosis triggered by proinflammatory cytokine, tumor necrosis factor (TNF)α. Through transcriptional induction of distinct subsets of cyto-protective target genes, NF-κB inhibits the execution of apoptosis activated by this cytokine. This protective action is mediated, in part, by factors (such as A20, GADD45β, and XIAP) that downregulate the pro-apoptotic c-Jun-N-terminal (JNK) pathway. A suppression of reactive oxygen species (ROS), which are themselves major cell death-inducing elements activated by TNFα, is an additional protective function recently ascribed to NF-κB. This function of NF-κB involves an induction of mitochondrial anti-oxidant enzyme, manganese superoxide dismutase (Mn-SOD), and a control of cellular iron availability through upregulation of Ferritin heavy chain - one of two subunits of Ferritin, the major iron storage protein complex of the cell. An emerging view of NF-κB is that, while integrated, its actions in immunity and in promoting cell survival are executed through upregulation of distinct subsets of target genes. Thus, these inducible blockers of apoptosis may provide potential new targets to inhibit specific functions of NF-κB. In the future, this might allow for a better treatment of complex human diseases involving dysregulated NF-κB activity, including chronic inflammatory conditions and cancer.
NF-κB/Rel转录因子因其在炎症和免疫调节中的作用而闻名。NF-κB还能阻断由促炎细胞因子、肿瘤坏死因子(TNF)α引发的程序性细胞死亡（PCD）或细胞凋亡。NF-κB通过转录诱导不同的细胞保护靶基因亚群，抑制由该细胞因子激活的细胞凋亡的执行。这种保护作用部分是由下调促凋亡c- jun - n末端（JNK）通路的因子（如A20、GADD45β和XIAP）介导的。活性氧（ROS）本身是TNFα激活的主要细胞死亡诱导因子，其抑制是NF-κB最近发现的一种额外的保护功能。NF-κ b的这种功能包括诱导线粒体抗氧化酶，锰超氧化物歧化酶（Mn-SOD），并通过上调铁蛋白重链（铁蛋白的两个亚基之一，细胞中主要的铁储存蛋白复合物）来控制细胞铁的可用性。一种关于NF-κB的新观点认为，当NF-κB被整合时，它在免疫和促进细胞存活方面的作用是通过上调不同的靶基因亚群来实现的。因此，这些诱导型细胞凋亡阻滞剂可能为抑制NF-κB的特定功能提供了潜在的新靶点。在未来，这可能有助于更好地治疗涉及NF-κB活性失调的复杂人类疾病，包括慢性炎症和癌症。
{"title":"In the Crosshairs: NF-κB Targets the JNK Signaling Cascade.","authors":"Can G Pham, Salvatore Papa, Concetta Bubici, Francesca Zazzeroni, Guido Franzoso","doi":"10.2174/156801405774933188","DOIUrl":"10.2174/156801405774933188","url":null,"abstract":"<p><p>NF-κB/Rel transcription factors are well-known for their roles in the regulation of inflammation and immunity. NF-κB also blocks programmed cell death (PCD) or apoptosis triggered by proinflammatory cytokine, tumor necrosis factor (TNF)α. Through transcriptional induction of distinct subsets of cyto-protective target genes, NF-κB inhibits the execution of apoptosis activated by this cytokine. This protective action is mediated, in part, by factors (such as A20, GADD45β, and XIAP) that downregulate the pro-apoptotic c-Jun-N-terminal (JNK) pathway. A suppression of reactive oxygen species (ROS), which are themselves major cell death-inducing elements activated by TNFα, is an additional protective function recently ascribed to NF-κB. This function of NF-κB involves an induction of mitochondrial anti-oxidant enzyme, manganese superoxide dismutase (Mn-SOD), and a control of cellular iron availability through upregulation of Ferritin heavy chain - one of two subunits of Ferritin, the major iron storage protein complex of the cell. An emerging view of NF-κB is that, while integrated, its actions in immunity and in promoting cell survival are executed through upregulation of distinct subsets of target genes. Thus, these inducible blockers of apoptosis may provide potential new targets to inhibit specific functions of NF-κB. In the future, this might allow for a better treatment of complex human diseases involving dysregulated NF-κB activity, including chronic inflammatory conditions and cancer.</p>","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"4 6","pages":"569-576"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760982/pdf/nihms110480.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28437519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2005-11-30DOI: 10.2174/156801405774933160
I. Todd, P. Tighe, R. Powell
{"title":"TNF and TNF Receptors in TRAPS","authors":"I. Todd, P. Tighe, R. Powell","doi":"10.2174/156801405774933160","DOIUrl":"https://doi.org/10.2174/156801405774933160","url":null,"abstract":"","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"46 3 1","pages":"577-585"},"PeriodicalIF":0.0,"publicationDate":"2005-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801405774933160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67902803","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}
Pub Date : 2005-11-30DOI: 10.2174/156801405774933197
L. Adorini, G. Penna, N. Giarratana, R. Mariani, M. Uskoković
{"title":"Inhibition of Type 1 Diabetes Development by Vitamin D Receptor Agonists","authors":"L. Adorini, G. Penna, N. Giarratana, R. Mariani, M. Uskoković","doi":"10.2174/156801405774933197","DOIUrl":"https://doi.org/10.2174/156801405774933197","url":null,"abstract":"","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"4 1","pages":"645-651"},"PeriodicalIF":0.0,"publicationDate":"2005-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801405774933197","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67902823","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}
Pub Date : 2005-11-30DOI: 10.2174/156801405774933151
R. Pedotti, L. Steinman
{"title":"Histamine in Immune Regulation: Possible Roles in Autoimmune Demyelinating Disease of the Central Nervous System","authors":"R. Pedotti, L. Steinman","doi":"10.2174/156801405774933151","DOIUrl":"https://doi.org/10.2174/156801405774933151","url":null,"abstract":"","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"4 1","pages":"637-643"},"PeriodicalIF":0.0,"publicationDate":"2005-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801405774933151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67902791","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}
Pub Date : 2005-11-30DOI: 10.2174/156801405774933115
D. Savage
{"title":"Transcriptional Control of Metabolism, Inflammation and the Immune Response: The Role of PPARs","authors":"D. Savage","doi":"10.2174/156801405774933115","DOIUrl":"https://doi.org/10.2174/156801405774933115","url":null,"abstract":"","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"4 1","pages":"631-635"},"PeriodicalIF":0.0,"publicationDate":"2005-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801405774933115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67903235","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}
Pub Date : 2005-11-30DOI: 10.2174/156801405774933205
G. Matarese, V. Rosa, Daniela Aufiero, C. Procaccini, C. Alviggi, G. Placido, S. Fontana, S. Zappacosta
{"title":"Adipokines, Metabolism and the Immune Response in the Regulation of Inflammation","authors":"G. Matarese, V. Rosa, Daniela Aufiero, C. Procaccini, C. Alviggi, G. Placido, S. Fontana, S. Zappacosta","doi":"10.2174/156801405774933205","DOIUrl":"https://doi.org/10.2174/156801405774933205","url":null,"abstract":"","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"13 1","pages":"619-624"},"PeriodicalIF":0.0,"publicationDate":"2005-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801405774933205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67902836","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}
Pub Date : 2005-11-30DOI: 10.2174/156801405774933133
N. Siegel
{"title":"All in the Family: The TNF-TNFR Superfamily in the Pathogenesis and Treatment of Rheumatoid Arthritis and other Inflammatory Diseases","authors":"N. Siegel","doi":"10.2174/156801405774933133","DOIUrl":"https://doi.org/10.2174/156801405774933133","url":null,"abstract":"","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"4 1","pages":"587-596"},"PeriodicalIF":0.0,"publicationDate":"2005-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801405774933133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67902767","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}
Pub Date : 2005-11-30DOI: 10.2174/156801405774933124
L. Sedger
Apoptotic cell death can be triggered by death-inducing cytokines such and TNFα, Fas Ligand, and TRAIL, and death-receptors TNF-Rs, Fas, and TRAIL-Rs, or by mitochondrial-sensed events. The biochemical signalling pathways that lead from death receptors or mitochondria to the degradation of DNA and apoptotic cell death are wellcharacterized. Furthermore, it is clear that apoptotic cell death is important for the normal biology in all organisms. Apoptotic cell death is equally important in the context of virus infection such that the induction of apoptosis appears to be a generalised innate response to the insult of virus infection. As a consequence, viral-mediated regulation of apoptosis is crucial for the successful replication and survival of most viruses. For this reason viruses have evolved multiple strategies to subvert the apoptotic response. This review summarises the mechanisms by which viral gene products inhibit the production of TNFα, the interaction between TNFα and TNF-Rs, the expression of TNF-Rs, and inhibit virtually all aspects of TNF-R signalling, including TNF-R-mediated apoptosis and TNF-R-mediated proliferation and inflammation. Current Medicinal Chemistry – Anti-Inflammatory and Anti-Allergy Agents (2005). In press.
{"title":"Viral Inhibition of Tumour Necrosis Factor-α (TNFα) and TNF-Receptor Induced Apoptosis and Inflammation","authors":"L. Sedger","doi":"10.2174/156801405774933124","DOIUrl":"https://doi.org/10.2174/156801405774933124","url":null,"abstract":"Apoptotic cell death can be triggered by death-inducing cytokines such and TNFα, Fas Ligand, and TRAIL, and death-receptors TNF-Rs, Fas, and TRAIL-Rs, or by mitochondrial-sensed events. The biochemical signalling pathways that lead from death receptors or mitochondria to the degradation of DNA and apoptotic cell death are wellcharacterized. Furthermore, it is clear that apoptotic cell death is important for the normal biology in all organisms. Apoptotic cell death is equally important in the context of virus infection such that the induction of apoptosis appears to be a generalised innate response to the insult of virus infection. As a consequence, viral-mediated regulation of apoptosis is crucial for the successful replication and survival of most viruses. For this reason viruses have evolved multiple strategies to subvert the apoptotic response. This review summarises the mechanisms by which viral gene products inhibit the production of TNFα, the interaction between TNFα and TNF-Rs, the expression of TNF-Rs, and inhibit virtually all aspects of TNF-R signalling, including TNF-R-mediated apoptosis and TNF-R-mediated proliferation and inflammation. Current Medicinal Chemistry – Anti-Inflammatory and Anti-Allergy Agents (2005). In press.","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"4 1","pages":"597-615"},"PeriodicalIF":0.0,"publicationDate":"2005-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801405774933124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67903245","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号