Abstract：
:Toll-like receptors (TLRs) play a fundamental role in the inflammatory response against invading pathogens. However, the dysregulation of TLR-signaling pathways is implicated in several autoimmune/inflammatory diseases. Here, we show that a novel small molecule TLR-inhibitor (TAC5) and its derivatives TAC5-a, TAC5-c, TAC5-d, and TAC5-e predominantly antagonized poly(I:C) (TLR3)-, imiquimod (TLR7)-, TL8-506 (TLR8)-, and CpG-oligodeoxynucleotide (TLR9)-induced signaling pathways. TAC5 and TAC5-a significantly hindered the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), reduced the phosphorylation of mitogen-activated protein kinases, and inhibited the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6. Besides, TAC5-a prevented the progression of psoriasis and systemic lupus erythematosus (SLE) in mice. Interestingly, TAC5 and TAC5-a did not affect Pam3CSK4 (TLR1/2)-, FSL-1 (TLR2/6)-, or lipopolysaccharide (TLR4)-induced TNF-α secretion, indicating their specificity towards endosomal TLRs (TLR3/7/8/9). Collectively, our data suggest that the TAC5 series of compounds are potential candidates for treating autoimmune diseases such as psoriasis or SLE.
journal_name
Cellsjournal_title
Cellsauthors
Patra MC,Achek A,Kim GY,Panneerselvam S,Shin HJ,Baek WY,Lee WH,Sung J,Jeong U,Cho EY,Kim W,Kim E,Suh CH,Choi Sdoi
10.3390/cells9071648subject
Has Abstractpub_date
2020-07-09 00:00:00issue
7issn
2073-4409pii
cells9071648journal_volume
9pub_type
杂志文章相关文献
Cells文献大全abstract：:YRNAs are a class of non-coding RNAs that are components of the Ro60 ribonucleoprotein particle and are essential for initiation of DNA replication. Ro60 ribonucleoprotein particle is a target of autoimmune antibodies in patients suffering from systemic lupus erythematosus and Sjögren's syndrome. Deregulation of YRNAs...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9051281
更新日期：2020-05-21 00:00:00
abstract：:Hepatic fibrosis is the consequence of an unresolved wound healing process in response to chronic liver injury and involves multiple cell types and molecular mechanisms. The hepatic endocannabinoid and apelin systems are two signalling pathways with a substantial role in the liver fibrosis pathophysiology-both are upr...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8111311
更新日期：2019-10-24 00:00:00
abstract：:Cotransplantation of mesenchymal stem cells (MSCs) with hematopoietic stem cells (HSCs) has been widely reported to promote HSC engraftment and enhance marrow stromal regeneration. The present study aimed to define whether MSC conditioned medium could recapitulate the effects of MSC cotransplantation. Mouse bone marro...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9010221
更新日期：2020-01-15 00:00:00
abstract：:Epithelial organs are the first barrier against microorganisms and genotoxic stress, in which the p53 family members p63 and p73 have both overlapping and distinct functions. Intriguingly, p73 displays a very specific localization to basal epithelial cells in human tissues, while p63 is expressed in both basal and dif...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells10010025
更新日期：2020-12-25 00:00:00
abstract：:Rab proteins compose the largest family of small GTPases and control the different steps of intracellular membrane traffic. More recently, they have been shown to also regulate cell signaling, division, survival, and migration. The regulation of these processes generally occurs through recruitment of effectors and reg...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8080909
更新日期：2019-08-16 00:00:00
abstract：:The knowledge about the molecular alterations which are found in head and neck squamous cell carcinomas (HNSCC) has much increased in recent years. However, we are still awaiting the translation of this knowledge to new diagnostic and therapeutic options. Among the many molecular changes that are detected in head and ...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9030723
更新日期：2020-03-15 00:00:00
abstract：:Immunotherapy has revolutionised the treatment of cancers by harnessing the power of the immune system to eradicate malignant tissue. However, it is well recognised that some cancers are highly resistant to these therapies, which is in part attributed to the immunosuppressive landscape of the tumour microenvironment (...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells10010056
更新日期：2021-01-01 00:00:00
abstract：:Recent studies have revealed synaptic dysfunction to be a hallmark of various psychiatric diseases, and that glial cells participate in synapse formation, development, and plasticity. Glial cells contribute to neuroinflammation and synaptic homeostasis, the latter being essential for maintaining the physiological func...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9102176
更新日期：2020-09-27 00:00:00
abstract：:Grade IV astrocytomas, or glioblastomas (GBMs), are the most common malignant primary brain tumor in adults. The median GBM patient survival of 12-15 months has remained stagnant, in spite of treatment strategies, making GBMs a tremendous challenge clinically. This is at least in part due to the complex interaction of...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8101203
更新日期：2019-10-05 00:00:00
abstract：:Animal growth requires coordination of cell growth and cell cycle progression with developmental signaling. Loss of cell cycle control is extremely detrimental, with reduced cycles leading to impaired organ growth and excessive proliferation, potentially resulting in tissue overgrowth and driving tumour initiation. Du...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells1041182
更新日期：2012-12-05 00:00:00
abstract：:Aging is associated with metabolic changes and low-grade inflammation in several organs, which may be due to NLRP3 inflammasome activation. Methods: Here, we asked whether age-related liver changes such as lipid metabolism and fibrosis are reduced in aged mice lacking the NLRP3 inflammasome. We report reduced protein ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9102148
更新日期：2020-09-23 00:00:00
abstract：:Evolutionarily conserved Notch plays a critical role in embryonic development and cellular self-renewal. It has both tumour suppressor and oncogenic activity, the latter of which is widely described. Notch-activating mutations are associated with haematological malignancies and several solid tumours including breast, ...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9061503
更新日期：2020-06-20 00:00:00
abstract：:Telomere comprises the ends of eukaryotic linear chromosomes and is composed of G-rich (TTAGGG) tandem repeats which play an important role in maintaining genome stability, premature aging and onsets of many diseases. Majority of the telomere are replicated by conventional DNA replication, and only the last bit of the...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9020359
更新日期：2020-02-04 00:00:00
abstract：:A number of oxylipins have been described as endogenous PPAR ligands. The very short biological half-lives of oxylipins suggest roles as autocrine or paracrine signaling molecules. While coronary arterial atherosclerosis is the root of myocardial infarction, aortic atherosclerotic plaque formation is a common readout ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9051096
更新日期：2020-04-29 00:00:00
abstract：:Poly(A)-specific ribonuclease (PARN), a multifunctional multi-domain deadenylase, is crucial to the regulation of mRNA turnover and the maturation of various non-coding RNAs. Despite extensive studies of the well-folding domains responsible for PARN catalysis, the structure and function of the C-terminal domain (CTD) ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8080836
更新日期：2019-08-05 00:00:00
abstract：:Network-based systems biology has become an important method for analyzing high-throughput gene expression data and gene function mining. Escherichia coli (E. coli) has long been a popular model organism for basic biological research. In this paper, weighted gene co-expression network analysis (WGCNA) algorithm was ap...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells7030019
更新日期：2018-03-08 00:00:00
abstract：:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries with almost 25% affected adults worldwide. The growing public health burden is getting evident when considering that NAFLD-related liver transplantations are predicted to almost double within the next 20 years. Typic...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8080845
更新日期：2019-08-07 00:00:00
abstract：:Infectious endocarditis (IE) remains one of the deadliest heart diseases with a high death rate, generally following thrombo-embolic events. Today, therapy is based on surgery and antibiotic therapy. When thromboembolic complications in IE patients persist, this is often due to our lack of knowledge regarding the path...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9081899
更新日期：2020-08-13 00:00:00
abstract：:The MRE11-RAD50-NBS1 (MRN) protein complex is one of the primary vehicles for repairing DNA double strand breaks and maintaining the genomic stability within the cell. The role of the MRN complex to recognize and process DNA double-strand breaks as well as signal other damage response factors is critical for maintaini...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9071678
更新日期：2020-07-13 00:00:00
abstract：:Successful RNAi applications depend on strategies allowing stable and persistent expression of minimal gene silencing triggers without perturbing endogenous gene expression. In this study, we proposed an endogenous microRNA (miRNA) cluster as a novel integration site for small hairpin RNAs (shRNAs). We successfully in...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8020113
更新日期：2019-02-01 00:00:00
abstract：:Lysosomal function has a central role in maintaining neuronal homeostasis, and, accordingly, lysosomal dysfunction has been linked to neurodegeneration and particularly to Parkinson's disease (PD). Lysosomes are the converging step where the substrates delivered by autophagy and endocytosis are degraded in order to re...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9112399
更新日期：2020-11-02 00:00:00
abstract：:Circular RNAs (circRNAs) are genome transcripts that are produced from back-splicing of specific regions of pre-mRNA. These single-stranded RNA molecules are widely expressed across diverse phyla and many of them are stable and evolutionary conserved between species. Growing evidence suggests that many circRNAs functi...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9061473
更新日期：2020-06-16 00:00:00
abstract：:Osteoarthritis (OA) is a degenerative and inflammatory joint disorder with cartilage loss. Dental pulp stem cells (DPSCs) can undergo chondrogenic differentiation and secrete growth factors associated with tissue repair and immunomodulation. Leukocyte- and platelet-rich fibrin (L-PRF) emerges in regenerative medicine ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9040980
更新日期：2020-04-15 00:00:00
abstract：:Background: Mucopolysaccharidosis type I-Hurler (MPS1-H) is a severe genetic lysosomal storage disorder due to loss-of-function mutations in the IDUA gene. The subsequent complete deficiency of alpha l-iduronidase enzyme is directly responsible of a progressive accumulation of glycosaminoglycans (GAG) in lysosomes whi...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9122593
更新日期：2020-12-03 00:00:00
abstract：:During embryonic development, the heart undergoes complex morphogenesis from a liner tube into the four chambers consisting of ventricles, atria and valves. At the same time, the cardiomyocytes compact into a dense, aligned, and highly vascularized myocardium. The extracellular matrix (ECM) is known to play an importa...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9020285
更新日期：2020-01-24 00:00:00
abstract：:The Drosophila ovary offers a suitable model system to study the mechanisms that orchestrate diverse cellular processes. Oogenesis starts from asymmetric stem cell division, proper differentiation and the production of fully patterned oocytes equipped with all the maternal information required for embryogenesis. Spati...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9020274
更新日期：2020-01-22 00:00:00
abstract：:The exposure of mouse embryos in utero and primary cortical neurons to ionizing radiation results in the P53-dependent activation of a subset of genes that is highly induced during brain development and neuronal maturation, a feature that these genes reportedly share with circular RNAs (circRNAs). Interestingly, some ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8080778
更新日期：2019-07-26 00:00:00
abstract：:Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCC), mainly caused by PTCH1 gene mutations. Our current study aimed to establish (1) PTCH1 germinal and somatic mutational status, (2) component and Hedgehog (HH) pathway targets gene expres...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8020144
更新日期：2019-02-11 00:00:00
abstract：:Human mesenchymal stromal/stem cells (hMSCs) show great promise in cell therapy due to their immunomodulatory properties. The overall immunomodulatory response of hMSCs resembles the resolution of inflammation, in which lipid mediators and regulatory macrophages (Mregs) play key roles. We investigated the effect of hM...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9092142
更新日期：2020-09-22 00:00:00
abstract：:The authors wish to make the following erratum to this paper [1].[...]. ...
journal_title：Cells
pub_type： 杂志文章,已发布勘误
doi：10.3390/cells5030036
更新日期：2016-09-20 00:00:00
