Abstract:
:Toll-like receptors (TLRs) play key roles in detecting pathogens and initiating inflammatory responses that, subsequently, prime specific adaptive responses. Several mechanisms control TLR activity to avoid excessive inflammation and consequent immunopathology, including the anti-inflammatory cytokine IL-10. Recently, several TLR-responsive microRNAs (miRs) have also been proposed as potential regulators of this signaling pathway, but their functional role during the inflammatory response still is incompletely understood. In this study, we report that, after LPS engagement, monocytes up-regulate miR-146b via an IL-10-mediated STAT3-dependent loop. We show evidence that miR-146b modulates the TLR4 signaling pathway by direct targeting of multiple elements, including the LPS receptor TLR4 and the key adaptor/signaling proteins myeloid differentiation primary response (MyD88), interleukin-1 receptor-associated kinase 1 (IRAK-1), and TNF receptor-associated factor 6 (TRAF6). Furthermore, we demonstrate that the enforced expression of miR-146b in human monocytes led to a significant reduction in the LPS-dependent production of several proinflammatory cytokines and chemokines, including IL-6, TNF-α, IL-8, CCL3, CCL2, CCL7, and CXCL10. Our results thus identify miR-146b as an IL-10-responsive miR with an anti-inflammatory activity based on multiple targeting of components of the TLR4 pathway in monocytes and candidate miR-146b as a molecular effector of the IL-10 anti-inflammatory activity.
journal_name
Proc Natl Acad Sci U S Aauthors
Curtale G,Mirolo M,Renzi TA,Rossato M,Bazzoni F,Locati Mdoi
10.1073/pnas.1219852110subject
Has Abstractpub_date
2013-07-09 00:00:00pages
11499-504issue
28eissn
0027-8424issn
1091-6490pii
1219852110journal_volume
110pub_type
杂志文章abstract::The neotropical Heliconius butterflies are famous examples of Müllerian mimicry, due to the diverse array of shared, brightly colored wing patterns that advertise the butterflies' unpalatability. The parallel geographical variation in these patterns within several widespread species has been invoked to support the con...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.14.6491
更新日期:1994-07-05 00:00:00
abstract::The Millennium Ecosystem Assessment (MA) introduced a new framework for analyzing social-ecological systems that has had wide influence in the policy and scientific communities. Studies after the MA are taking up new challenges in the basic science needed to assess, project, and manage flows of ecosystem services and ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0808772106
更新日期:2009-02-03 00:00:00
abstract::Although the applicability of small subunit ribosomal RNA (16S rRNA) sequences for bacterial classification is now well accepted, the general use of these molecules has been hindered by the technical difficulty of obtaining their sequences. A protocol is described for rapidly generating large blocks of 16S rRNA sequen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.20.6955
更新日期:1985-10-01 00:00:00
abstract::Selective harvest of large individuals should alter natural adaptive landscapes and drive evolution toward reduced somatic growth and increased reproductive investment. However, few studies have simultaneously considered the relative importance of artificial and natural selection in driving trait changes in wild popul...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0705908104
更新日期:2007-10-02 00:00:00
abstract::P201 is a short (eight-residue) nonacidic peptide that comprises a strong transcriptional activating region when tethered to DNA in yeast. Here we identify the mediator protein Gal11 as an essential target of P201. Deletion of Gal11, which modestly decreases activation elicited by the typical acidic yeast activator, a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.092263499
更新日期:2002-06-25 00:00:00
abstract::Virus population growth depends on contacts between viruses and their hosts. It is often unclear how sufficient contacts are made between viruses and their specific hosts to generate spikes in viral abundance. Here, we show that copepods, acting as predators, can bring aquatic viruses and their algal hosts into contac...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1613843113
更新日期:2016-11-29 00:00:00
abstract::Membraneless organelles contain a wide spectrum of molecular chaperones, indicating their important roles in modulating the metastable conformation and biological function of membraneless organelles. Here we report that class I and II Hsp40 (DNAJ) proteins possess a high ability of phase separation rendered by the fle...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2002437117
更新日期:2020-12-08 00:00:00
abstract::We have previously described a gene delivery system based upon the receptor-mediated endocytosis of DNA complexed with transferrin-polycation conjugates. This delivery system has been found to be very effective for both the internalization and the expression of genetic material in cells that have many transferrin rece...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.10.4255
更新日期:1991-05-15 00:00:00
abstract::In making sense of the visual world, the brain's processing is driven by two factors: the physical information provided by the eyes ("bottom-up" data) and the expectancies driven by past experience ("top-down" influences). We use degraded stimuli to tease apart the effects of bottom-up and top-down processes because t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1111224109
更新日期:2012-05-15 00:00:00
abstract::We present data that demonstrate that three MR elements isolated from wild populations of Drosophila melanogaster on two continents can cause large deletions of the X chromosome in males. The deleted chromosomes, termed mini-X chromosomes, are induced at a frequency of approximately 1:4000 in chromosomes that are init...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.13.4533
更新日期:1987-07-01 00:00:00
abstract::Band 3, the major intrinsic protein of the human erythrocyte membrane, was specifically labeled with the covalent fluorescent probe eosin isothiocyanate. The lateral mobility of labeled band 3 in the plane of the membrane under various conditions of ionic strength and temperature was examined by using the fluorescence...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.5.2537
更新日期:1980-05-01 00:00:00
abstract::When the dog kidney Na+/K+-transporting ATPase (EC 3.6.1.37, formerly EC 3.6.1.3) was labeled with an ATP analogue, 5'-(p-fluorosulfonyl)benzoyladenosine (FSBA), there was a concomitant loss of ATPase activity. The presence of ATP protected the enzyme from both labeling and inactivation. The ATP-sensitive incorporatio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.7.2071
更新日期:1986-04-01 00:00:00
abstract::The aldosterone-induced augmentation of Na+ transport in toad bladder was analyzed by comparing the hormonal actions on the transepithelial short-circuit current and on the amiloride-sensitive 22Na+ uptake in isolated membrane vesicles. Incubating bladders with 0.5 microM aldosterone for 3 hr evoked more than a 2-fold...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.19.7413
更新日期:1988-10-01 00:00:00
abstract::Stimulation by isoproterenol causes large increases in the activity of rat pineal N-acetyltransferase (arylamine acetyltransferase or acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) after a variable lag period. Lengthening periods of exposure to light cause rapid increases in the sensitivity of pineal N-acetyltr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.5.1661
更新日期:1975-05-01 00:00:00
abstract::The occurrence and sequelae of disorders that lead to hypoxic spells such as asthma, chronic obstructive pulmonary disease, and obstructive sleep apnea (OSA) exhibit daily variance. This prompted us to examine the interaction between the hypoxic response and the circadian clock in vivo. We found that the global transc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1914112117
更新日期:2020-01-07 00:00:00
abstract::The physiological significance of multiple G-protein-coupled receptor subtypes, such as the beta-adrenergic receptors (beta ARs), remains obscure, since in many cases several subtypes activate the same effector and utilize the same physiological agonists. We inspected the deduced amino acid sequences of the beta AR su...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.8.3665
更新日期:1993-04-15 00:00:00
abstract::T cells must respond differently to antigens of varying affinity presented at different doses. Previous attempts to map peptide MHC (pMHC) affinity onto T-cell responses have produced inconsistent patterns of responses, preventing formulations of canonical models of T-cell signaling. Here, a systematic analysis of T-c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1608820113
更新日期:2016-10-25 00:00:00
abstract::We have previously shown that geographic differences in cancer mortalities in Europe are related to (in order of importance): geographic distances (reflecting environmental differences), ethnohistoric distances (encompassing cultural and genetic attributes), and genetic distances of the populations in the areas studie...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.11.6067
更新日期:2000-05-23 00:00:00
abstract::We have isolated two recombinant cDNAs whose corresponding RNAs have an increased abundance in scrapie-infected hamster brain. DNA sequence analysis has shown that these two recombinants represent the genes for sulfated glycoprotein 2 and transferrin. The abundance of sulfated glycoprotein 2 RNA is increased in hippoc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.18.7260
更新日期:1989-09-01 00:00:00
abstract::We have studied the reaction dynamics for HgI(2) in methanol by using time-resolved x-ray diffraction (TRXD). Although numerous time-resolved spectroscopic studies have provided ample information about the early dynamics of HgI(2), a comprehensive reaction mechanism in the solution phase spanning from picoseconds up t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0601958103
更新日期:2006-06-20 00:00:00
abstract::Interleukin 3 (IL-3) stimulates the proliferation and differentiation of various haematopoietic progenitor cells. Recently, IL-3 and other cytokines were reported to exert a neurotrophic activity and to be associated with neurological disorders, suggesting their complex role in the central nervous system. We now show ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.19.11354
更新日期:1998-09-15 00:00:00
abstract::The skeletal muscle L-type Ca2+ channel is a complex of five subunits that is specifically localized in the triad. Its primary function is the rapid activation of Ca2+ release from cytoplasmic stores in a process called excitation-contraction coupling. To study the role of alpha1S-beta1a interactions in the incorporat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.9.5015
更新日期:1998-04-28 00:00:00
abstract::The biological function of Glu-181 in the photoactivation process of rhodopsin is explored through spectroscopic studies of site-specific mutants. Preresonance Raman vibrational spectra of the unphotolyzed E181Q mutant are nearly identical to spectra of the native pigment, supporting the view that Glu-181 is uncharged...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1531970100
更新日期:2003-08-05 00:00:00
abstract::Junctional Adhesion Molecule-A (JAM-A) is a transmembrane adhesive protein expressed at endothelial junctions and in leukocytes. Here we report that JAM-A is required for the correct infiltration of polymorphonuclear leukocytes (PMN) into an inflamed peritoneum or in the heart upon ischemia-reperfusion injury. The def...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0500147102
更新日期:2005-07-26 00:00:00
abstract::The human gamma herpesviruses, Kaposi sarcoma-associated virus (KSHV) and EBV, are associated with multiple cancers. Recent evidence suggests that EBV and possibly other viruses can manipulate the tumor microenvironment through the secretion of specific viral and cellular components into exosomes, small endocytically ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1303906110
更新日期:2013-07-30 00:00:00
abstract::2-Isopropylmalate synthase (EC 4.1.3.12) of yeast is a mitochondrial enzyme. We now provide evidence showing that a large part of the 2-isopropylmalate synthase activity that is associated with the mitochondria is located in the mitochondrial matrix. In vitro translation of total yeast RNA followed by immunoprecipitat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.5.1270
更新日期:1983-03-01 00:00:00
abstract::A series of small peptides corresponding to the amino termini of the fibrin alpha- and beta-chains has been synthesized. The peptides glycyl-L-prolyl-L-arginyl-L-proline and glycyl-L-prolyl-L-arginylsarcosine are potent inhibitors of fibrin polymerization. Moreover, these peptides have a natural stability stemming fro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.7.3085
更新日期:1978-07-01 00:00:00
abstract::Long-term memory relies on modulation of synaptic connections in response to experience. This plasticity involves trafficking of AMPA receptors (AMPAR) and alteration of spine morphology. Arc, a gene induced by synaptic activity, mediates the endocytosis of AMPA receptors and is required for both long-term and homeost...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1006546107
更新日期:2010-10-19 00:00:00
abstract::Most higher eukaryotic tubulins are separated into alpha- and beta-tubulin when electrophoresed in NaDodSO4- denaturing gels, while many lower eukaryotic tubulins are poorly resolved under these conditions, which include a stacking gel (pH 6.80) and a separating gel (pH 8.80). By lowering the pH of the separating gel ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.20.6908
更新日期:1985-10-01 00:00:00
abstract::Purified human platelet-derived growth factor (PDGF) induces an increase in amino acid uptake via system A in quiescent human diploid fibroblasts. Cells must be exposed to PDGF for 45 min to obtain maximum transport stimulation. Transport stimulation requires protein synthesis. Transient exposure to PDGF, alone, in th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.10.3203
更新日期:1982-05-01 00:00:00