Abstract:
:Activation of TLR4 by lipopolysaccharide (LPS) induces both pro-inflammatory and anti-inflammatory cytokine production in macrophages. Type 4 phosphodiesterases (PDE4) are key cAMP-hydrolyzing enzymes, and PDE4 inhibitors are considered as immunosuppressors to various inflammatory responses. We demonstrate here that PDE4 inhibitors enhance the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) secretion in LPS-activated mouse peritoneal macrophages, and this response was regulated at the transcriptional level rather than an increased IL-1Ra mRNA stability. Studies with PDE4-deficient macrophages revealed that the IL-1Ra upregulation elicited by LPS alone is PKA-independent, whereas the rolipram-enhanced response was mediated by inhibition of only PDE4B, one of the three PDE4 isoforms expressed in macrophages, and it requires PKA but not Epac activity. However, both pathways activate CREB to induce IL-1Ra expression. PDE4B ablation also promoted STAT3 phosphorylation (Tyr705) to LPS stimulation, but this STAT3 activation is not entirely responsible for the IL-1Ra upregulation in PDE4B-deficient macrophages. In a model of LPS-induced sepsis, only PDE4B-deficient mice displayed an increased circulating IL-1Ra, suggesting a protective role of PDE4B inactivation in vivo. These findings demonstrate that PDE4B negatively modulates anti-inflammatory cytokine expression in innate immune cells, and selectively targeting PDE4B should retain the therapeutic benefits of nonselective PDE4 inhibitors.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Yang JX,Hsieh KC,Chen YL,Lee CK,Conti M,Chuang TH,Wu CP,Jin SCdoi
10.1038/srep46165subject
Has Abstractpub_date
2017-04-06 00:00:00pages
46165issn
2045-2322pii
srep46165journal_volume
7pub_type
杂志文章abstract::Circulating miRNAs have attracted attention as serum biomarkers for several diseases. In this study, we aimed to evaluate the diagnostic value of circulating miRNA-21 (miR-21) as a novel biomarker for elderly patients with type 2 cardiorenal syndrome (CRS-2). A total of 157 elderly patients with chronic heart failure ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-61836-z
更新日期:2020-03-17 00:00:00
abstract::Detailed characterization and mapping of oligonucleotide function in vivo is generally a very time consuming effort that only allows for hypothesis driven subsampling of the full sequence to be analysed. Recent advances in deep sequencing together with highly efficient parallel oligonucleotide synthesis and cloning te...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep37563
更新日期:2016-11-22 00:00:00
abstract::Diagnostic testing often assesses the cardiovascular or respiratory systems in isolation, ignoring the major pathophysiologic interactions between the systems in many diseases. When both systems are assessed currently, multiple modalities are utilized in costly fashion with burdensome logistics and decreased accessibi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-04676-8
更新日期:2017-07-13 00:00:00
abstract::Coastal protection design heights typically consider the superimposed effects of tides, surges, waves, and relative sea-level rise (SLR), neglecting non-linear feedbacks between these forcing factors. Here, we use hydrodynamic modelling and multivariate statistics to show that shallow coastal areas are extremely sensi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep40171
更新日期:2017-01-06 00:00:00
abstract::In the fifty years since the postulation of Moore's Law, the increasing energy consumption in silicon electronics has motivated research into emerging devices. An attractive research direction is processing information via the phase of spin waves within magnonic-logic circuits, which function without charge transport ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-08114-7
更新日期:2017-08-11 00:00:00
abstract::A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-018-32187-7
更新日期:2018-09-26 00:00:00
abstract::A new energy dispersive X-ray absorption spectroscopy (EDXAS) method is presented for simultaneous wide-field imaging and transmission X-ray absorption spectroscopy (XAS) to enable rapid imaging and speciation of elements. Based on spectral K-Edge Subtraction imaging (sKES), a bent Laue imaging system diffracting in t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-54287-8
更新日期:2019-11-27 00:00:00
abstract::Electroencephalographic hyperscanning was used to investigate interbrain synchronization patterns in dyads of participants interacting through speech. Results show that brain oscillations are synchronized between listener and speaker during oral narratives. This interpersonal synchronization is mediated in part by a l...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-04464-4
更新日期:2017-06-23 00:00:00
abstract::The Antarctic silverfish (Pleuragramma antarctica) is a critically important forage species with a circumpolar distribution and is unique among other notothenioid species for its wholly pelagic life cycle. Previous studies have provided mixed evidence of population structure over regional and circumpolar scales. The a...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-36030-x
更新日期:2018-12-14 00:00:00
abstract::Rodents are important reservoir hosts of many important zoonotic viruses. The family Picornaviridae contains clinically important pathogens that infect humans and animals, and increasing numbers of rodent picornaviruses have recently been associated with zoonoses. We collected 574 pharyngeal and anal swab specimens fr...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep34381
更新日期:2016-09-29 00:00:00
abstract::Polycyclic aromatic hydrocarbons (PAHs) pollutions often occur in marine and other saline environment, largely due to anthropogenic activities. However, study of the PAHs-degradation genotypes in halophiles is limited, compared with the mesophilic terrestrial PAHs degraders. In this study, a bacterial consortium (CY-1...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-12979-z
更新日期:2017-10-02 00:00:00
abstract::Photoswitchable fluorescent proteins with controllable light-dark states and spectral shifts in emission in response to light have led to breakthroughs in the study of cell biology. Nevertheless, conventional photoswitching is not applicable for weakly fluorescent proteins and requires UV light with low depth penetrat...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep36417
更新日期:2016-11-08 00:00:00
abstract::c-FLIP (cellular FLICE-inhibitory protein) is the pivotal regulator of TRAIL resistance in cancer cells, It is a short-lived protein degraded through the ubiquitin/proteasome pathway. The discovery of factors and mechanisms regulating its protein stability is important for the comprehension of TRAIL resistance by tumo...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep22999
更新日期:2016-03-14 00:00:00
abstract::Savant syndrome is a phenomenon whereby individuals with cognitive impairments have one or more outstanding abilities, inconsistent with their general intellectual functioning. Approximately 50% of savant individuals have autism spectrum disorder (ASD), and 10-30% of people with ASD have savant skills. To shed additio...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-59209-7
更新日期:2020-02-10 00:00:00
abstract::Gene overexpression through the targeting of transcription activation domains to regulatory DNA via catalytically defective Cas9 (dCas9) represents a powerful approach to investigate gene function as well as the mechanisms of gene control. To date, the most efficient dCas9-based activator is the Synergistic Activation...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-54179-x
更新日期:2019-12-02 00:00:00
abstract::Toll-like receptors (TLRs) recognise microbes that contribute to the severity of bronchiolitis and the subsequent risk of asthma. We evaluated whether post-bronchiolitis asthma was associated with polymorphisms in the TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084, and TLR10 rs4129009 gen...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-03429-x
更新日期:2017-06-07 00:00:00
abstract::In spite of its prevalence in animals and plants, endogenous nitric oxide (NO) has been rarely reported in fungi. We present here our observations on production of intracellular NO and its possible roles during development of Neurospora crassa, a model filamentous fungus. Intracellular NO was detected in hypha 8-16 ho...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep30037
更新日期:2016-07-18 00:00:00
abstract::Using analytical expressions for the magnetization textures of thin submicron-sized magnetic cylinders in vortex state, we derive closed-form algebraic expressions for the ensuing small-angle neutron scattering (SANS) cross sections. Specifically, for the perpendicular and parallel scattering geometries, we have compu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep25055
更新日期:2016-04-26 00:00:00
abstract::We combine matter-wave interferometry and cavity optomechanics to propose a coherent matter-light interface based on mechanical motion at the quantum level. We demonstrate a mechanism that is able to transfer non-classical features imprinted on the state of a matter-wave system to an optomechanical device, transducing...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep03378
更新日期:2013-11-29 00:00:00
abstract::With the reduction of oil and gas reserves and the increase of mining difficulty in Northern China, the carbonate rocks in Southern North China Basin are becoming a significant exploration target for carbonate reservoirs. However, the development characteristics, formation stages, formation environments and mechanisms...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-80878-x
更新日期:2021-01-12 00:00:00
abstract::Aftershocks are the most striking evidence of earthquake interactions and the physical mechanisms at the origin of their occurrence are still intensively debated. Novel insights stem from recent results on the influence of the faulting style on the aftershock organisation in magnitude and time. Our study shows that th...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep15560
更新日期:2015-10-26 00:00:00
abstract::We tested the hypothesis that epigenetic mechanisms in the brain and the immune system are associated with chronic pain. Genome-wide DNA methylation assessed in 9 months post nerve-injury (SNI) and Sham rats, in the prefrontal cortex (PFC) as well as in T cells revealed a vast difference in the DNA methylation landsca...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep19615
更新日期:2016-01-28 00:00:00
abstract::Heparan sulfate (HS) is a polysaccharide known to modulate many important biological processes, including Wnt signaling. However, the biochemical interaction between HS and Wnt molecules is not well characterized largely due to the lack of suitable methods. To determine the Wnt binding domain in HS, we used a Wnt sign...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep26245
更新日期:2016-05-17 00:00:00
abstract::The role of the Androgen Receptor (AR) expression and its activity in the prognosis of hepatocellular carcinoma (HCC) remains inconclusive. The aim of this study is to analyze the role of the AR expression and its activity as prognostic biomarkers in HCC. Three-hundred and thirty-seven patients from The Cancer Genome ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-79177-2
更新日期:2020-12-16 00:00:00
abstract::Hematopoietic stem/progenitor cells (HSPC) in zebrafish emerge from the aortic hemogenic endothelium (HE) and migrate towards the caudal hematopoietic tissue (CHT), where they expand and differentiate during definitive hematopoiesis. Phospholipase C gamma 1 (Plcγ1) has been implicated for hematopoiesis in vivo and in ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-36338-8
更新日期:2019-01-21 00:00:00
abstract::The original motivation of the article is to give a systematic investigation on the protocol of combining computer simulation and accurate synthesis of serial peptide protected gold clusters for potent tumor targeting therapy. Glutathione peroxidase-1 (GPx-1) is a crucial antioxidant selenoenzyme that regulates cellul...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-00278-6
更新日期:2017-03-09 00:00:00
abstract::The Maxwellian near-eye displays have attracted growing interest in various applications. By using a confined pupil, a Maxwellian display presents an all-in-focus image to the viewer where the image formed on the retina is independent of the optical power of the eye. Despite being a promising technique, current Maxwel...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-55346-w
更新日期:2019-12-10 00:00:00
abstract::Quantum physics is undoubtedly the most successful theory of the microscopic world, yet the complexities which arise in applying it even to simple atomic and molecular systems render the description of basic collision probabilities a formidable task. For this reason, approximations are often employed, the validity of ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-33425-8
更新日期:2018-10-10 00:00:00
abstract::In this study, nanowires/nanowalls were generated on a silicon wafer through a chemical etching method. Octadecyltrichlorosilane (OTS) was deposited onto the nanowire/nanowall surfaces to alter their hydrophobicity. The hydrophobic characteristics of the surfaces were further modified via a 1.5-μm-thick layer of n-oct...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep38678
更新日期:2016-12-09 00:00:00
abstract::The pulsed events of rainstorm erosion on the Loess Plateau are well-known, but little information is available concerning the characteristics of superficial soil erosion processes caused by heavy rainstorms at the watershed scale. This study statistically evaluated characteristics of pulsed runoff-erosion events base...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-22045-x
更新日期:2018-02-27 00:00:00