Abstract：
:Interferon-α (IFNα) has enormous potential for anti-proliferative and anti-viral treatments. However, clinical success is still hampered due to its limited bioavailability and thus, lack of sustained modulation of disease-relevant protective programs. Consequently, we here examined whether IFNα immobilized on nanoscale ferromagnetic R-Chitosan carriers is capable of inducing rapid and sustained activation of STAT1 signaling. We report the spontaneous formation of a stable nanoparticle-IFNα protein corona, which was exploited to generate IFNα-loaded spheres, obviating the need to specifically couple the cytokine to the nanoparticles (NPs). Notably, comprehensive experimental approaches ensure that formation of the IFNα NP-corona does not affect the biological activity of the cytokine, as STAT1 signaling was efficiently activated. Employing human prostate cancer and melanoma cell models, we found that the intensity and duration of STAT1 phosphorylation as well as the downstream activation of pathobiologically relevant genes were dose and particle dependent. In comparison with free IFNα, IFNα-loaded spheres resulted in a more sustained biologically relevant STAT1 activation, demonstrated also by conferring innate cellular immunity against vesicular stomatitis virus (VSV) infection. For one, our study demonstrates the advantages of biodegradable IFNα-coated R-Chitosan NPs for controlled cytokine release, and thereby improved therapy. Second, we reveal that the permanent presence of IFNα and not just the initial STAT1 phosphorylation ensures sustained IFNα-dependent signaling.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Pollok S,Ginter T,Günzel K,Pieper J,Henke A,Stauber RH,Reichardt W,Krämer OHdoi
10.1016/j.cellsig.2013.01.012subject
Has Abstractpub_date
2013-04-01 00:00:00pages
989-98issue
4eissn
0898-6568issn
1873-3913pii
S0898-6568(13)00015-6journal_volume
25pub_type
杂志文章abstract：:Inflammation is characterized by early influx of polymorphonuclear neutrophils (PMNs), followed by a second wave of monocyte recruitment. PMNs mediate monocyte recruitment via their release of heparin binding protein (HBP), which activates CCR2 (CC-chemokine receptor 2) on monocytes. However, the pathways for such sig...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2017.12.008
更新日期：2018-03-01 00:00:00
abstract：:Protein phosphatases play a key role in balancing the cellular responses to the transforming growth factor-β (TGFβ) signals. Several protein phosphatases have been attributed roles in the regulation of the TGFβ pathway. Among these, PPM1A is the only phosphatase reported to dephosphorylate SMAD2/3 in the nucleus. Howe...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.07.003
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abstract：:Actinomycin D and nutlin-3a (A + N) activate p53, partly through induction of phosphorylation on Ser392. The death of A549 cells induced by A + N morphologically resembles inflammation-inducing pyroptosis - cell destruction triggered by activated caspase-1. The treatment with A + N (or camptothecin) strongly upregulat...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2020.109552
更新日期：2020-05-01 00:00:00
abstract：:In this study we investigated the release of Ca2+ in brain microsomes after Ca2+ loading by the Ca(2+)-ATPase or by the Na+/Ca2+ exchanger. The results show that in microsomes loaded with Ca2+ by the Ca(2+)-ATPase, Ins(1,4,5)P3 (5 microM) released 21 +/- 2% of the total Ca2+ accumulated, and that in the microsomes loa...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(92)90049-e
更新日期：1992-11-01 00:00:00
abstract：:The role of the ras oncogene in the signalling pathway triggered by platelet-derived growth factor BB (PDGF-BB) has been investigated in a cell line which normally differentiates into myotubes. Following the activation of the N-ras oncogene, however, the cells proliferate and form foci. PDGF-BB stimulated the phosphor...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(94)00082-m
更新日期：1995-03-01 00:00:00
abstract：:Proliferation of mammalian cells both in vivo and in vitro is dependent upon physiological concentrations of extracellular Ca2+. Growth factor stimulation of quiescent cells at the G0/G1 border usually results in a rapid mobilization of Ca2+ from both intra- and extracellular pools. However, Ca2+ influx is also requir...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/0898-6568(94)00074-l
更新日期：1995-02-01 00:00:00
abstract：:The protective effect of Regulator of G protein Signaling 2 (RGS2) in cardiac hypertrophy is thought to occur through its ability to inhibit the chronic GPCR signaling that promotes pathogenic growth both in vivo and in cultured cardiomyocytes. However, RGS2 is known to have additional functions beyond its activity as...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.02.006
更新日期：2014-06-01 00:00:00
abstract：:Self-renewing divisions of normal and cancerous stem cells are responsible for the initiation and maintenance of normal and certain cancerous tissues, respectively. Recent findings suggest that tumor surveillance mechanisms can reduce regenerative capacity and frequency of normal stem cells, thereby contributing to ti...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2007.06.021
更新日期：2007-12-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(93)90038-n
更新日期：1993-11-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.08.028
更新日期：2014-12-01 00:00:00
abstract：:TMPRSS4 is a novel type II transmembrane serine protease that is highly expressed in pancreatic, thyroid, colon, and other cancer tissues. Previously, we demonstrated that TMPRSS4 mediates tumor cell invasion, migration, and metastasis. However, the mechanisms by which TMPRSS4 contributes to invasion are not fully und...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.08.002
更新日期：2014-02-01 00:00:00
abstract：:Alzheimer's disease (AD) is a neurodegenerative illness and the leading cause of dementia in the elderly. The accumulation of amyloid-β peptide (Aβ) is a well-known pathological hallmark associated with the disease. However, Aβ is only one of several metabolites produced by β- and γ-secretase actions on the transmembr...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2011.10.007
更新日期：2012-02-01 00:00:00
abstract：:The transforming growth factor beta (TGFbeta) family of growth regulatory peptides plays an important role in the regulation of gastrointestinal epithelial cell homeostasis. Loss of growth inhibitory signalling by TGFbeta is common in the context of Ras-transformation and it has been hypothesized that loss of TGFbeta ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(03)00010-x
更新日期：2003-07-01 00:00:00
abstract：:In fura-2 loaded isolated mouse pancreatic acinar cells, xanthine oxidase (XOD)-catalyzed reactive oxygen species (ROS) generation caused an increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)) by release of Ca(2+) from intracellular stores. The ROS-induced Ca(2+) signals showed large variability in shape and ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(01)00247-9
更新日期：2002-02-01 00:00:00
abstract：:alpha-Thrombin activates several G-proteins including members of the Gq, Gi, and G12/13 families, although the physiological importance of these proteins is still not completely understood. We specifically investigated the role of Gq alpha in modulating alpha-thrombin-induced mitogenesis. In Gqa1 cells, a stable cell ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(01)00279-0
更新日期：2002-06-01 00:00:00
abstract：:Phospholipase D (PLD) is involved in diverse cellular processes including cell movement, adhesion, and vesicle trafficking through cytoskeletal rearrangements. However, the mechanism by which PLD induces cytoskeletal reorganization is still not fully understood. Here, we describe a new link to cytoskeletal changes tha...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.03.014
更新日期：2011-08-01 00:00:00
abstract：:The nuclear factor kappa B (NF-κB) transcription factor-mediated transcription is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli. Both the proteolytic and non-proteolytic functions of ubiquitination are critically important for the regulation of NF-κB activation. L...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.11.017
更新日期：2011-04-01 00:00:00
abstract：:The small GTPase Rac1 plays a pivotal role in insulin-stimulated glucose uptake in skeletal muscle, which is mediated by GLUT4 translocation to the plasma membrane. However, regulatory mechanisms for Rac1 and its role in the signaling pathway composed of phosphoinositide 3-kinase and the serine/threonine kinase Akt re...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.02.023
更新日期：2013-06-01 00:00:00
abstract：:The ERBB1/2/4 inhibitor neratinib causes plasma membrane-associated K-RAS to mislocalize into intracellular vesicles; this effect is enhanced by HDAC inhibitors and the combination of [neratinib + sodium valproate] is now a phase I trial (NCT03919292). The present studies were performed to understand resistance mechan...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2020.109525
更新日期：2020-04-01 00:00:00
abstract：:Antidepressants are commonly used in the treatment of anxiety and depression, medical conditions that affect approximately 17-20% of the population. The clinical effects of antidepressants take several weeks to manifest, suggesting that these drugs induce adaptive changes in brain structures affected by anxiety and de...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2004.12.007
更新日期：2005-05-01 00:00:00
abstract：:The role of microtubules (MTs) in steroid hormone-dependent human glucocorticoid receptor (hGR) activation/translocation is controversial. It was demonstrated recently that colchicine (COL) down-regulates hGR-driven genes in primary human hepatocytes by a mechanism involving inhibition of hGR translocation to the nucl...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2004.06.010
更新日期：2005-02-01 00:00:00
abstract：:Insulin is an inducer of brown fat adipogenesis through the activation of a signalling network that involves positive/negative modulators. Given the importance of brown adipose tissue (BAT) for basal thermogenic energy expenditure, we investigated the role of PTP1B in the acquisition of terminal differentiated phenoty...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2009.11.019
更新日期：2010-04-01 00:00:00
abstract：:HOX family transcription factors belong to a highly conserved subgroup of the homeobox superfamily that determines cellular fates in embryonic morphogenesis and the maintenance of adult tissue architecture. HOX family transcription factors play key roles in numerous cellular processes including cell growth, differenti...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2019.109469
更新日期：2020-02-01 00:00:00
abstract：BACKGROUND:All identified mammalian TRPC channels show a C-terminal calmodulin (CaM)- and inositol 1,4,5-trisphosphate receptors (IP(3)Rs)-binding (CIRB) site involved in the regulation of TRPC channel function. OBJECTIVES:To assess the basis of CaM/IP(3)Rs binding to the CIRB site of TRPC6 and its role in platelet ph...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.06.022
更新日期：2011-11-01 00:00:00
abstract：:Human Glioblastoma is one deadly disease; the median survival time is reported to be 13.9 months after treatment. In the present study, we discovered that DHX33 is highly expressed in 84% of all Glioblastoma multiforme (GBM). Knockdown of DHX33 led to significant reduced proliferation and migration in glioblastoma cel...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.12.005
更新日期：2019-02-01 00:00:00
abstract：:Inflammatory stimulus during development increases the risk for adverse neurologic outcome. One possible mechanism is disrupting neuronal migration. Using lipopolysaccharide (LPS)-treatment to assess inflammatory stimulus on neuronal migration of cerebellar granule neurons, we previously found that LPS-activation incr...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.10.017
更新日期：2011-02-01 00:00:00
abstract：:Cyclic mechanical stretch associated with pulsatile blood pressure can modulate cytoskeletal remodeling and intracellular signaling in vascular endothelial cells. The aim of this study was to evaluate the role of stretch-induced actin stress fiber orientation in intracellular signaling involving the activation of c-ju...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2006.02.008
更新日期：2006-11-01 00:00:00
abstract：:High levels of VEGF and leptin are strongly linked to worse prognosis of breast cancer. Leptin signalling upregulates VEGF in human and mouse mammary tumor cells (MT), but the specific molecular mechanisms are largely unknown. Pharmacologic and genetic approaches were used to dissect the mechanism of leptin regulation...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.05.003
更新日期：2010-09-01 00:00:00
abstract：:15-lipoxygenase (15-LO) is known to play an important role in chronic pulmonary hypertension. Accumulating evidence for its down-stream participants in the vasoconstriction and remodeling processes of pulmonary arteries, while how hypoxia regulates 15-LO/15-hydroxyeicosatetraenoic acid (15-HETE) to mediate hypoxic pul...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.06.007
更新日期：2012-10-01 00:00:00
abstract：:Nephrin, an important structural and signal molecule of podocyte slit-diaphragm (SD), has been suggested to contribute to the angiotensin II (Ang II)-induced podocyte injury. Caveolin-1 has been demonstrated to play a crucial role in signaling transduction. In the present study, we evaluated the role of caveolin-1 in ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.09.022
更新日期：2012-02-01 00:00:00
