Receptors and clinical investigation最新文献

{"title":"Microbial DNA regulates intestinal homeostasis via the AIM2 inflammasome","authors":"S. Waliullah, M. Harris, H. Zaki","doi":"10.14800/RCI.1268","DOIUrl":"https://doi.org/10.14800/RCI.1268","url":null,"abstract":"Absent in melanoma 2 (AIM2) is a cytosolic DNA sensor which upon activation assembles a multiprotein complex called the inflammasome. Previous studies have shown that several inflammasome-forming pattern recognition receptors exhibit a protective function against inflammatory bowel disease and colorectal cancer. However, the role of AIM2 in sensing intestinal microbial DNA and regulating inflammatory responses therein was unknown. In a recent study published in Cell Reports, we demonstrated that Aim2 -/- mice are highly susceptible to experimental colitis which was associated with a defect in the inflammasome activation as indicated by reduced caspase-1 cleavage and decreased production of IL-1b and IL-18. We also studied the underlying mechanism of AIM2 inflammasome-mediated protection against intestinal injury and inflammation. We found that the inflammasome downstream cytokine IL-18 contributes to intestinal homeostasis via induction of antimicrobial peptides, such as Reg3b, Reg3g, Lcn2, S100A8, and S100A9 in intestinal epithelial cells. As a consequence of the defective production of antimicrobial peptides, Aim2 -/- and other inflammasome-deficient mice harbor altered microbiota in the intestine as characterized by significantly higher burden of Escherichia coli. This research highlight will provide an overview of our findings and discuss how sensing of microbial DNA by AIM2 maintains intestinal homeostasis.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"503 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78716129","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":"Functional consequences of genetic polymorphisms in the NKG2D receptor signaling pathway and putative gene interactions","authors":"Antje Isernhagen, D. Malzahn, S. Monecke, D. Schilling, P. Shah, G. Multhoff, G. Wulf, D. Kube, H. Bickeböller, R. Dressel","doi":"10.14800/RCI.1269","DOIUrl":"https://doi.org/10.14800/RCI.1269","url":null,"abstract":"NKG2D (NK group 2, member D) is an activating natural killer (NK) receptor, which is expressed on NK and CD8 + T cells. On NK cells, NKG2D elicits cytotoxicity and release of cytokines. On CD8 + T cells, it functions as a co-stimulatory molecule. The receptor recognizes several ligands including the major histocompatibility complex (MHC) class I chain-related molecules A (MICA) and B (MICB) as well as the UL16-binding proteins (ULBP). The diversity of NKG2D ligands is further increased by a high degree of genetic variability of the ligands. Recently, an amino acid exchange from valine to methionine at position 129 in MICA has been found to be associated with the outcome of allogeneic hematopoietic stem cell transplantation (HSCT), and the functional consequences of this specific genetic variation have been elucidated. The clinical associations found after HSCT were explainable by the functional differences of the MICA-129 variants. Herein, we discuss how the genetic polymorphisms of NKG2D ligands and NKG2D itself interact and may affect the outcome of HSCT and the susceptibility to other diseases, which have been associated with polymorphisms in the NKG2D signaling pathway.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79477440","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":"Molecular basis of shikonin-induced immunogenic cell death: insights for developing cancer therapeutics","authors":"N. Yang, Tien-Jen Lin","doi":"10.14800/RCI.1234","DOIUrl":"https://doi.org/10.14800/RCI.1234","url":null,"abstract":"Shikonin, a natural plant product isolated from the herb Lithospermum erythrorhizon, has been found to strongly stimulate immunogenic cell death (ICD) of tumor cells, which induced a potent immune response by dendritic cells (DCs) to suppress tumor growth and/or metastasis. Recently, specific intracellular protein targets including heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and pyruvate kinase-M2 (PKM2) have been demonstrated to act as candidate receptors for shikonin. Among them, direct binding-interference with hnRNPA1 was found to be critical for shikonin-induced immunogenicity of mammary tumor cells, which can result in strong suppression of tumor metastasis. Mechanistic studies have further revealed that specific damage-associated molecular patterns (DAMPs) associated with immunogenicity, including heat shock proteins 70 (HSP-70), calreticulin (CRT) and high mobility group box 1 (HMGB1) in tumor cell lysate (TCL), can play important and comprehensive roles in activating specific immunities of tumor cell lysate (TCL)-pulsed DCs. In this brief review article, we present these findings together and further provide a molecular mode of action as the pharmacological basis of SK-induced ICD.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81622316","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":"An) orexigenic hypothalamic neuropeptides are differentially expressed in high and low feed efficient quail lines","authors":"Kaley Blankenship, E. Greene, W. Bottje, N. Anthony, S. Dridi","doi":"10.14800/RCI.1218","DOIUrl":"https://doi.org/10.14800/RCI.1218","url":null,"abstract":"The livestock and poultry industry is facing numerous challenges to keep up with the increasing demand for high quality animal protein due to the continuously increasing global human population, severe drought conditions around the world, and grains being used for ethanol production. Since feed costs are the majority of the total cost required to produce a live bird, feed efficiency (FE) is a trait of importance. It is beneficial to develop a more deep molecular understanding of the mechanisms that determine feed efficiency. Recently, this study used Japanese quail that were divergently selected for high and low feed efficiency as a model to determine the differential expression of several feeding-related hypothalamic neuropeptides.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74170261","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":"Anti-aging effect of magnesium lithospermate β from Salvia miltiorrhiza Bunge on skin","authors":"E. Lee, T. Yokozawa, Takashi Tanaka, Nam Deuk, B. Yu, H. Chung","doi":"10.14800/RCI.1191","DOIUrl":"https://doi.org/10.14800/RCI.1191","url":null,"abstract":"Magnesium lithospermate B (MLB, also called salvianolic acid B), one of the hydrophilic phenolic compounds of Salvia miltiorrhiza Bunge has been reported to possess numerous health benefits, but a role for MLB in the prevention of skin aging has not been fully explored. In a recent publication, we reported that the skin anti-aging action of MLB depends on its ability to suppress collagen degradation via its anti-oxidant activity, and subsequently, to increase the expressions of type I and III collagen genes through PPARb/d activation. For this research highlight, we describe the salient findings from our recent study on the anti-wrinkle effect of MLB and the molecular mechanism underlying its skin anti-aging action.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"103 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89284907","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":"Signal transduction of Interleukin-11 and Interleukin-6 α-Receptors","authors":"J. Lokau, C. Garbers","doi":"10.14800/RCI.1190","DOIUrl":"https://doi.org/10.14800/RCI.1190","url":null,"abstract":"The cytokines Interleukin (IL)-11 and IL-6 are important mediators that regulate differentiation and proliferation of immune cells. Both cytokines bind to unique non-signaling α-receptors (IL-11R and IL-6R, respectively), and the resulting cytokine/cytokine receptor complexes recruit a homodimer of the signal-transducing β-receptor glycoprotein (gp)130. Gp130 is expressed ubiquitously, whereas both α-receptors show a cell- and tissue-specific expression pattern, thus determining cellular responsiveness towards IL-6 and/or IL-11. Formation of the signaling complexes activates intracellular signaling cascades, most prominently the Janus kinase (Jak)/Signal Transducer and Activator of Transcription (STAT) pathway. In a recent paper published in Biochimie, we analyzed the signaling capacity of eight chimeric receptors consisting of different domains of IL-11R and IL-6R. Our results showed that the intracellular region, the transmembrane region or the stalk region can be swapped between the two receptors, as they are not essential to discriminate between the two cytokines. Selectivity of the two receptors is exclusively warranted by the cytokine binding module (CBM), which resides within the domains D1 to D3. These results underline a modular organization of IL-11R and IL-6R and a comparable signal transduction of both cytokines.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75262736","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":"Anti-interleukin and associated receptors monoclonal antibodies therapy in autoimmune diseases","authors":"S. Tavakolpour","doi":"10.14800/RCI.1173","DOIUrl":"https://doi.org/10.14800/RCI.1173","url":null,"abstract":"There are nearly 40 approved monoclonal antibodies (mABs) in the U.S. for different diseases. These drugs are increasingly using in different autoimmune diseases, including rheumatoid arthritis (RA), asthma, psoriasis, systemic lupus erythematosus (SLE), atopic dermatitis (AD), multiple sclerosis (MS), and type 1 diabetes (T1D). Several phase 2 and 3 studies reported the clinical improvement due to treating with mABs. However, some adverse events (AEs) such as infections, injection-site reactions are frequently reported. In addition to approved diseases, off-label uses also led to some new results, which may cause reviewing the drug for other diseases. In this review, it was tried to discuss on the role of mABs that target interleukins or their associated receptors in treatment of autoimmune diseases. Moreover, approval statues, efficiency, safety and the possible associated AEs of the mABs on the market, based on the least clinical trials were also discussed.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91240649","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":"Wnt signaling in idiopathic carpal tunnel syndrome","authors":"Y. Yamanaka, K. Menuki, Y. Zenke, H. Hirasawa, A. Sakai","doi":"10.14800/RCI.1122","DOIUrl":"https://doi.org/10.14800/RCI.1122","url":null,"abstract":"Carpal tunnel syndrome (CTS) is the most frequently reported entrapment neuropathy; however, the exact pathological mechanism of CTS remains unknown. In a recent paper published in the Journal of Orthopaedic Research, we investigated the associations between Wnt signaling and the etiology of idiopathic CTS (ICTS). We compared the expression levels of genes encoding Wnt1, 2, 3, 4, 5a, 5b, 6, 7a, 7b, 8a, 8b, 9a, 9b, 10a, 10b, 11, and 16 in the flexor tenosynovium between ICTS patients and controls, and we also evaluated whether an association exists between Wnt signaling and cell proliferation factors, such as estrogen-responsive finger protein, epidermal growth factor receptor, heparin binding-epidermal growth factor-like growth factor, insulin-like growth factor-1, and vascular endothelial growth factor (VEGF). To compare the cell proliferation potency, expression levels of MIB-1 protein were also measured. We found that Wnt9a gene expression in the flexor tenosynovium is more prominent in ICTS patients. A positive correlation was observed in only ICTS patient group for the gene expression of Wnt9a and VEGF in the flexor tenosynovium. There were no relationships between the expression levels of Wnt9a and fibroblast proliferation in either group. These results indicate that Wnt9a may be involved in the expression of VEGF in ICTS.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82344196","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 antagonist SPECT tracer 123I-iododexetimide binds preferentially to the muscarinic M1 receptor in-vivo, but is it also a potential tool to assess the occupancy of muscarinic M1 receptors by agonists?","authors":"G. Bakker, Nora Chekrouni, W. Vingerhoets, J. V. Wieringen, K. Bruin, J. Eersels, J. D. Jonge, Y. Chahid, O. Bloemen, T. Amelsvoort, J. Booij","doi":"10.14800/RCI.1163","DOIUrl":"https://doi.org/10.14800/RCI.1163","url":null,"abstract":"Cognitive deterioration in neuropsychiatric disorders is associated with high attrition rates giving an urgent need to develop better pharmaceutical therapies. The underlying mechanisms of cognitive impairments are unclear but research has shown that the muscarinic receptor subtype 1 (M 1 receptor ) plays a critical role. Blocking the M 1 receptor gives rise to profound cognitive deficits, while the administration of M 1 agonist drugs improves cognitive functioning. In this research highlight we will outline supporting data that the radiotracer 123 I-iododexetimide preferentially binds to the M 1 receptor in-vivo and can be used to assess changes in M 1 receptor expression in-vivo associated with cognitive decline. These findings come from a previously published paper extensively examining binding characteristics of 123/127 I-iododexetimide to muscarinic receptors. Results of biodistribution studies also has shown that acute administration of the M 1 / 4 receptor agonist xanomeline could inhibit 127 I-iododexetimide binding in M 1 -rich brain areas in rats, suggesting that 123 I-iododexetimide may also be used to evaluate the occupancy of M 1 receptors by M 1 agonists in-vivo. This may be of clinical relevance considering the efficacy of M 1 agonist drugs in the treatment of cognitive deficits. Here we show the results from new biodistribution experiments in rats conducted to test the hypothesis that 123 I-iododexetimide may be a useful radiotracer to evaluate the M 1 receptor occupancy by M 1 agonists in-vivo. Contrary to our expectations, no significant change in 123 I-iododexetimide ex-vivo binding was observed after acute administration of xanomeline in M 1 receptor-rich brain areas, whereas significantly decreased 123 I-iododexetimide binding was found after chronic treatment with xanomeline. 123 I-iododexetimide single photon emission computed tomography (SPECT) may therefore be a useful imaging tool to further evaluate M 1 receptor changes in neuropsychiatric disorders, as a potential stratifying biomarker, to assess the occupancy of M 1 receptors after M 1 antagonist treatment, or after chronic treatment with M 1 agonists, although it may be less suited to evaluate the M 1 receptor occupancy after acute treatment with M 1 agonists. Future studies should concentrate efforts towards finding also an M 1 agonist radiotracer for positron emission tomography (PET) or SPECT to assess the working mechanism of M 1 agonists.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"211 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81963399","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 role of estrogen receptors in intestinal homeostasis and disease","authors":"N. Choijookhuu, S. Hino, Phyu Synn Oo, Baatarsuren Batmunkh, Y. Hishikawa","doi":"10.14800/RCI.1109","DOIUrl":"https://doi.org/10.14800/RCI.1109","url":null,"abstract":"Estrogen has a pivotal role in many biological functions in both reproductive and non-reproductive organs, mediating actions through its receptors, estrogen receptor α (ERα) and ERβ. The expression of ERs is widespread in the body and is implicated in normal physiological processes as well as in disease conditions, including intestinal diseases. Immunohistochemical and functional analyses have revealed that ERβ is the predominant ER type in intestinal tract, but not ERα. The ERβ mediates to provide protection against duodenal ulcer, inflammatory bowel disease and colon cancer but may also contribute to the progression of constipation. In this review, we summarize the recent findings regarding estrogen and its receptors and their role in intestinal diseases. Based on these findings, it is possible to drive the pathogenesis of intestinal diseases using ER-subtype selective inhibitors or stimulators.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"195 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82800469","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}