Pub Date : 2005-01-31DOI: 10.2174/1568014053005363
J. Masumoto, N. Inohara
Nod proteins are defined as proteins carrying nucleotide-oligomerization domains (NODs) and are involved in regulation of immune responses and apoptosis. The Nod protein family contains 23 human members including Nod1, Nod2, cryopyrin, Ipaf, Apaf-1 and CIITA, as well as thousands of plant proteins, which are involved in pathogen-specific defense responses. A Nod protein generally contains an amino-termina l domain for binding downstream effector molecules, a central NOD and a carboxyl-terminal ligand recognition domain (LRD). Nod1 and Nod2 are involved in host recognition of small molecules that are components of bacterial peptidoglycan and activate nuclear factor κB (NF-κB) in response to sensing these molecules. This NF-κB activation occurs in a RICK- and IKK-dependent manner. The core ligand structure for Nod2 is muramyl dipeptide, a structural motif common in all bacteria, whereas the ligand for Nod1 is a dipeptide designated as iE-DAP, a motif found in only certain subgroups of bacteria. These molecules and their derivatives mediate host innate responses against bacteria and also function as immunostimula tory adjuvants through induction of cytokine secretion and co-stimulatory molecule expression. Although the mechanism is unknown, genetic and functional defects of Nod proteins are associated with several inflammatory diseases and immunodeficiency. These include susceptibility for Crohn's disease and Blau syndrome (Nod2), three related inflammatory diseases (cryopyrin) and type II bare lymphocyte syndrome (CIITA). Functional analyses of mutant Nod proteins suggest a common molecular basis for these diseases.
{"title":"The Molecular Functions of Nod Proteins and their Associated Diseases","authors":"J. Masumoto, N. Inohara","doi":"10.2174/1568014053005363","DOIUrl":"https://doi.org/10.2174/1568014053005363","url":null,"abstract":"Nod proteins are defined as proteins carrying nucleotide-oligomerization domains (NODs) and are involved in regulation of immune responses and apoptosis. The Nod protein family contains 23 human members including Nod1, Nod2, cryopyrin, Ipaf, Apaf-1 and CIITA, as well as thousands of plant proteins, which are involved in pathogen-specific defense responses. A Nod protein generally contains an amino-termina l domain for binding downstream effector molecules, a central NOD and a carboxyl-terminal ligand recognition domain (LRD). Nod1 and Nod2 are involved in host recognition of small molecules that are components of bacterial peptidoglycan and activate nuclear factor κB (NF-κB) in response to sensing these molecules. This NF-κB activation occurs in a RICK- and IKK-dependent manner. The core ligand structure for Nod2 is muramyl dipeptide, a structural motif common in all bacteria, whereas the ligand for Nod1 is a dipeptide designated as iE-DAP, a motif found in only certain subgroups of bacteria. These molecules and their derivatives mediate host innate responses against bacteria and also function as immunostimula tory adjuvants through induction of cytokine secretion and co-stimulatory molecule expression. Although the mechanism is unknown, genetic and functional defects of Nod proteins are associated with several inflammatory diseases and immunodeficiency. These include susceptibility for Crohn's disease and Blau syndrome (Nod2), three related inflammatory diseases (cryopyrin) and type II bare lymphocyte syndrome (CIITA). Functional analyses of mutant Nod proteins suggest a common molecular basis for these diseases.","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"4 1","pages":"43-51"},"PeriodicalIF":0.0,"publicationDate":"2005-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568014053005363","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67902495","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 : 2005-01-31DOI: 10.2174/1568014053005390
A. Shibuya, S. Tahara-Hanaoka, K. Shibuya
{"title":"DNAM-1 (CD226): A Two-Sword Fencer for Innate and Adaptive Immunity","authors":"A. Shibuya, S. Tahara-Hanaoka, K. Shibuya","doi":"10.2174/1568014053005390","DOIUrl":"https://doi.org/10.2174/1568014053005390","url":null,"abstract":"","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"4 1","pages":"53-58"},"PeriodicalIF":0.0,"publicationDate":"2005-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568014053005390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67902551","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 : 2005-01-31DOI: 10.2174/1568014053005345
N. Suzuki, Shinobu Suzuki, T. Saito
Toll-like receptors (TLRs), interleukin 1 receptor (IL-1R), IL-18 receptor (IL-18R) and plant R are vital to the induction of acute inflammation as well as various adaptive immune responses upon invasion of microorganisms. These receptors share a common cytoplasmic domain called the TIR (TLR/IL-1R/plant R) domain and the signaling cascade involving the TIR domain is conserved from invertebrate to vertebrate. The engagement of TIR domain containing receptors initiates their signaling through several intermediate proteins including serine-threonine kinase IL-1 receptor associated kinases (IRAKs). The IRAK family has four members and the newest member, IRAK-4, is indispensable to the TIR-mediated signaling pathway. The improper regulation of TIR receptor signaling leads to the development of such severe inflammatory diseases as sepsis, asthma, rheumatoid arthritis and even cancer. Therefore, it is very important to determine precisely the implications of TIR signaling in those inflammatory diseases for appropriate medical treatment and drug development. As IRAK-4 is the critical molecule for TIR-mediated signaling, it is a promising therapeutic target for many inflammatory diseases. In this review, we discuss the functions of the IRAK family members with focus on IRAK-4, to seek the possibility of yielding new therapeutic strategies.
{"title":"IRAKs: Key Regulatory Kinases of Innate Immunity","authors":"N. Suzuki, Shinobu Suzuki, T. Saito","doi":"10.2174/1568014053005345","DOIUrl":"https://doi.org/10.2174/1568014053005345","url":null,"abstract":"Toll-like receptors (TLRs), interleukin 1 receptor (IL-1R), IL-18 receptor (IL-18R) and plant R are vital to the induction of acute inflammation as well as various adaptive immune responses upon invasion of microorganisms. These receptors share a common cytoplasmic domain called the TIR (TLR/IL-1R/plant R) domain and the signaling cascade involving the TIR domain is conserved from invertebrate to vertebrate. The engagement of TIR domain containing receptors initiates their signaling through several intermediate proteins including serine-threonine kinase IL-1 receptor associated kinases (IRAKs). The IRAK family has four members and the newest member, IRAK-4, is indispensable to the TIR-mediated signaling pathway. The improper regulation of TIR receptor signaling leads to the development of such severe inflammatory diseases as sepsis, asthma, rheumatoid arthritis and even cancer. Therefore, it is very important to determine precisely the implications of TIR signaling in those inflammatory diseases for appropriate medical treatment and drug development. As IRAK-4 is the critical molecule for TIR-mediated signaling, it is a promising therapeutic target for many inflammatory diseases. In this review, we discuss the functions of the IRAK family members with focus on IRAK-4, to seek the possibility of yielding new therapeutic strategies.","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"4 1","pages":"13-20"},"PeriodicalIF":0.0,"publicationDate":"2005-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568014053005345","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67902483","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 : 2005-01-31DOI: 10.2174/1568014053005264
A. Chin, P. Dempsey, G. Cheng
The Receptor interacting protein-2 (Rip2, also called RICK, CARDIAK) is an intracellular serine-threonine kinase that contains a carboxy-termin al caspase activation and recruitment domain (CARD). The initial biochemical analysis emphasized a role for Rip2 in the activation of nuclear factor-kappaB (NF-κB) and apoptosis when overexpressed. The subsequent generation of mice with a targeted deletion of the gene for Rip2 and the description of a possible target for Rip2 kinase activity has clarified the role of Rip2. Following infectious challenges, the activation of a protective immune response relies on the coordinated interplay of contextual stimulation and inflammatory processes. All mammals must balance the need to combat dangerous pathogens from the destructive potential for mistaking autologous cells or proteins as appropriate targets for response. Rip2 has carved out an evolutionary niche serving as a regulator of inflammatory responses. Rip2 helps to direct or propagate signals towards cell-mediated immune responses and resolution of infection by modifying signals from pathogen recognition receptors (PRRs) such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (Nod) family members of innate immunity, the T cell receptor (TCR) complex of acquired immunity, and cytokine signaling of the interleukin (IL)-1 receptor family and IL-12 signaling pathways. Here we wish to outline the progress made in describing the biological significance of Rip2 and the mode of regulation of this kinase. Further studies considering Rip2 as a target of intervention have the potential to be of great clinical value.
受体相互作用蛋白-2 (Rip2，也称为RICK, CARDIAK)是一种细胞内丝氨酸-苏氨酸激酶，含有羧基端半胱天冬酶激活和募集结构域(CARD)。最初的生化分析强调了Rip2在过表达时对核因子κ b (NF-κB)的激活和细胞凋亡的作用。随后产生的Rip2基因靶向缺失小鼠，以及对Rip2激酶活性可能靶点的描述，已经阐明了Rip2的作用。在感染挑战之后，保护性免疫反应的激活依赖于环境刺激和炎症过程的协调相互作用。所有哺乳动物都必须平衡对抗危险病原体的需要，避免将自身细胞或蛋白质误认为适当的反应目标。Rip2已经开辟了一个进化利基，作为炎症反应的调节器。Rip2通过改变来自病原体识别受体(PRRs)的信号，如toll样受体(TLRs)和先天免疫的核苷酸结合寡聚化结构域(Nod)家族成员、获得性免疫的T细胞受体(TCR)复合物、白细胞介素(IL)-1受体家族和IL-12信号通路的细胞因子信号，帮助指导或传播细胞介导的免疫反应和感染的解决。在这里，我们希望概述在描述Rip2的生物学意义和这种激酶的调节模式方面取得的进展。将Rip2作为干预靶点的进一步研究可能具有很大的临床价值。
{"title":"Rip2: A Key Molecule that Regulates both Innate and Acquired Immunity","authors":"A. Chin, P. Dempsey, G. Cheng","doi":"10.2174/1568014053005264","DOIUrl":"https://doi.org/10.2174/1568014053005264","url":null,"abstract":"The Receptor interacting protein-2 (Rip2, also called RICK, CARDIAK) is an intracellular serine-threonine kinase that contains a carboxy-termin al caspase activation and recruitment domain (CARD). The initial biochemical analysis emphasized a role for Rip2 in the activation of nuclear factor-kappaB (NF-κB) and apoptosis when overexpressed. The subsequent generation of mice with a targeted deletion of the gene for Rip2 and the description of a possible target for Rip2 kinase activity has clarified the role of Rip2. Following infectious challenges, the activation of a protective immune response relies on the coordinated interplay of contextual stimulation and inflammatory processes. All mammals must balance the need to combat dangerous pathogens from the destructive potential for mistaking autologous cells or proteins as appropriate targets for response. Rip2 has carved out an evolutionary niche serving as a regulator of inflammatory responses. Rip2 helps to direct or propagate signals towards cell-mediated immune responses and resolution of infection by modifying signals from pathogen recognition receptors (PRRs) such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (Nod) family members of innate immunity, the T cell receptor (TCR) complex of acquired immunity, and cytokine signaling of the interleukin (IL)-1 receptor family and IL-12 signaling pathways. Here we wish to outline the progress made in describing the biological significance of Rip2 and the mode of regulation of this kinase. Further studies considering Rip2 as a target of intervention have the potential to be of great clinical value.","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"8 13 1","pages":"35-42"},"PeriodicalIF":0.0,"publicationDate":"2005-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568014053005264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67901895","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 : 2005-01-31DOI: 10.2174/1568014053005273
J. Ríos, E. Bas, M. Recio
Some medicinal plants, which are known to produce allergic reactions, are also specifically used as anti- inflammatory agents. Among the more relevant plants, we report species with cinnamaldehyde, cinnamic alcohol, geraniol, hydroxycitronellal, eugenol and isoeugenol are all potential allergens. In addition, fragrances, which are mixtures of small-molecul ar-weight compounds, may induce allergic contact dermatitis due to fragrance-spe cific CD4 + and CD8 + T lymphocytes. Plants from the Asteraceae family used in folk medicine as anti-inflamma tories can cause allergic contact dermatitis because of its content in sesquiterpene lactones, which have been reported as the anti- inflammatory principles in this species. Species with flavonoids, iridoids, terpenoids and alkaloids have been described as inhibitors of contact dermatitis. Scrophularia auriculata, Poria cocos, Santolina chamaecyparissus, Ranunculus sceleratus and Helichrysum italicum all showed activity in different experimental protocols of contact dermatitis, thus justifying the potential use of these medicinal plants as anti-allergens and inhibitors of contact dermatitis reactions produced by allergens and chemicals. Hydroquinone derivatives such as 1-O-β-glucopyranosyl-2-(3'-hydroxymethyl-3'-methylallyl) hydroquinone and arbutin, flavonoids such as kaempferol, apigenin and genistein, sesquiterpene lactones such as helenalin, diterpenes such as triptonide, triterpenes such as tripterine and bryonolic acid, iridoids such as scrovalentinoside, alkaloids such as indirubin, dehydrocorydaline, magnoflorine hydroxide and phellodendrine acetate, and polysaccharides such as fucoidin have been reported as inhibitors of contact dermatitis reactions.
{"title":"Effects of Natural Products on Contact Dermatitis","authors":"J. Ríos, E. Bas, M. Recio","doi":"10.2174/1568014053005273","DOIUrl":"https://doi.org/10.2174/1568014053005273","url":null,"abstract":"Some medicinal plants, which are known to produce allergic reactions, are also specifically used as anti- inflammatory agents. Among the more relevant plants, we report species with cinnamaldehyde, cinnamic alcohol, geraniol, hydroxycitronellal, eugenol and isoeugenol are all potential allergens. In addition, fragrances, which are mixtures of small-molecul ar-weight compounds, may induce allergic contact dermatitis due to fragrance-spe cific CD4 + and CD8 + T lymphocytes. Plants from the Asteraceae family used in folk medicine as anti-inflamma tories can cause allergic contact dermatitis because of its content in sesquiterpene lactones, which have been reported as the anti- inflammatory principles in this species. Species with flavonoids, iridoids, terpenoids and alkaloids have been described as inhibitors of contact dermatitis. Scrophularia auriculata, Poria cocos, Santolina chamaecyparissus, Ranunculus sceleratus and Helichrysum italicum all showed activity in different experimental protocols of contact dermatitis, thus justifying the potential use of these medicinal plants as anti-allergens and inhibitors of contact dermatitis reactions produced by allergens and chemicals. Hydroquinone derivatives such as 1-O-β-glucopyranosyl-2-(3'-hydroxymethyl-3'-methylallyl) hydroquinone and arbutin, flavonoids such as kaempferol, apigenin and genistein, sesquiterpene lactones such as helenalin, diterpenes such as triptonide, triterpenes such as tripterine and bryonolic acid, iridoids such as scrovalentinoside, alkaloids such as indirubin, dehydrocorydaline, magnoflorine hydroxide and phellodendrine acetate, and polysaccharides such as fucoidin have been reported as inhibitors of contact dermatitis reactions.","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"4 1","pages":"65-80"},"PeriodicalIF":0.0,"publicationDate":"2005-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568014053005273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67901402","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 : 2005-01-31DOI: 10.2174/1568014053005282
K. Taniguchi
{"title":"NKT Cells: A Regulator in Both Innate and Acquired Immunity","authors":"K. Taniguchi","doi":"10.2174/1568014053005282","DOIUrl":"https://doi.org/10.2174/1568014053005282","url":null,"abstract":"","PeriodicalId":88233,"journal":{"name":"Current medicinal chemistry. Anti-inflammatory & anti-allergy agents","volume":"4 1","pages":"59-64"},"PeriodicalIF":0.0,"publicationDate":"2005-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568014053005282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67901452","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}
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