Abstract:
:The dialysis of human and mouse neutrophils in patch clamp experiments in the conventional whole-cell mode induces the emergence of a chloride (Cl-) current that appeared to be primarily regulated by cytoplasmic ionic strength. The characteristics of this current resembled that of the classical, and ubiquitous volume-sensitive outwardly rectifying Cl- current: strong outward rectification, selectivity sequence of the Eisenman1 type, insensitivity to external pH and strong inhibition by tamoxifen, DCPIB and WW781. We show that this current is essentially supported by the leucine rich repeat containing 8 A (LRRC8A); the naturally occurring LRRC8A truncation mutant in ebo/ebo mice drastically reduced Cl- conductance in neutrophils. Remarkably, the residual component presents a distinct pharmacology, but appears equally potentiated by reduced ionic strength. We have investigated the role of the LRRC8A-supported current in the ionic homeostasis of the phagosomal compartment. The vacuolar pH, measured using SNARF-1 labeled Candida albicans, normally rises because of NADPH oxidase activity, and this elevation is blocked by certain Cl- channel inhibitors. However, the pH rise remains intact in neutrophils from the ebo/ebo mice which also demonstrate preserved phagocytic and respiratory burst capacities and normal-sized vacuoles. Thus, the LRRC8A-dependent conductance of neutrophils largely accounts for their "swell activated" Cl- current, but is not required for homeostasis of the phagosomal killing compartment.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Behe P,Foote JR,Levine AP,Platt CD,Chou J,Benavides F,Geha RS,Segal AWdoi
10.3389/fphar.2017.00262subject
Has Abstractpub_date
2017-05-12 00:00:00pages
262issn
1663-9812journal_volume
8pub_type
杂志文章abstract::Dysregulation of the complement system is central to age-related macular degeneration (AMD), the leading cause of blindness in the developed world. Most of the genetic variation associated with AMD resides in complement genes, with the greatest risk associated with polymorphisms in the complement factor H (CFH) gene; ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.591908
更新日期:2020-11-26 00:00:00
abstract::Saikosaponin d (SSd) is a major hepatoprotective component of saikosaponins derived from Radix Bupleuri, which was also linked to hepatotoxicity. Previous studies have demonstrated that caspases play a key role in SSd-induced liver cell death. Our in vitro and in vivo studies also showed that treatment with caspase in...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00732
更新日期:2018-07-06 00:00:00
abstract:Background:Acetylcholinesterase inhibitors (AChE-I) are recommended for the treatment of cognitive symptoms but also of behavioral and psychological symptoms in dementia. They are widely used not only in Alzheimer's disease, but also in other forms of dementia. Efficacy of treatment might depend on serum concentration ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00691
更新日期:2020-05-21 00:00:00
abstract::Field independence (FI) has been found to correlate with a wide range of cognitive processes requiring cognitive restructuring. Cognitive restructuring, that is going beyond the information given by the setting, is pivotal in creating stable mental representations of the environment, the so-called "cognitive maps," an...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00496
更新日期:2017-07-25 00:00:00
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00550
更新日期:2020-05-04 00:00:00
abstract::Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of protein aggregates (namely Lewy bodies) in dopaminergic neurons in the substantia nigra region of the brain. Alpha-synuclein (α-syn) is the major component of Lewy bodies in PD patients, and impairment of...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00016
更新日期:2019-01-28 00:00:00
abstract::Arsenic is a toxic environmental contaminant. Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been revealed by short time ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01176
更新日期:2019-10-11 00:00:00
abstract::The need for novel drugs for the treatment of autoimmune diseases is high, since available pharmaceuticals often have substantial side effects and limited efficacy. Natural products are a good starting point in the development of immunosuppressive leads. Since enhanced T cell proliferation is a common feature of autoi...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00402
更新日期:2020-04-08 00:00:00
abstract::We explored the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on CCl4-induced liver fibrosis with respect to the intestinal hepatic axis using a rat model. Histopathological staining results showed that DOP alleviated extensive fibrous tissue proliferation in interstitium and lessened intestinal mu...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00240
更新日期:2020-03-12 00:00:00
abstract::Upon interaction, neutrophils can potentially release neutrophil extracellular traps (NETs) on the surface of an implanted electrospun template, which may be a significant preconditioning event for implantable biomaterials of yet unknown consequences. In this study, we investigated the potential of polydioxanone templ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00289
更新日期:2018-03-28 00:00:00
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2014.00005
更新日期:2014-01-27 00:00:00
abstract::Breast cancer (BC) is one of the most prevalent types of cancer worldwide with high morbidity and mortality rates. Treatment modalities include systemic therapy, in which chemotherapy is a major component in many cases. Several chemotherapeutic agents are used in combinations or as single agents with many adverse even...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00445
更新日期:2020-04-15 00:00:00
abstract::Atherosclerotic cardiovascular disease (CVD) is a lipid-driven chronic inflammatory disease, in which macrophages are responsible for taking up these lipids and driving disease progression. Over the years, we and others have uncovered key pathways that regulate macrophage number/function and identified how metabolic d...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00666
更新日期:2019-06-13 00:00:00
abstract::Rheumatoid arthritis is an autoimmune disease characterized by synovial hyperplasia and progressive joint destruction. As reported previously, recombinant human endostatin (rhEndostatin) is associated with inhibition of joint bone destruction present in rat adjuvant-induced arthritis; however, the effect of rhEndostat...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00145
更新日期:2016-06-01 00:00:00
abstract::Cucurbitacin C (CuC), a novel analogue of triterpenoids cucurbitacins, confers a bitter taste in cucumber. Genes and signaling pathways responsive for biosynthesis of CuC have been identified in the recent years. In the present study, we explored the anti-cancer effects of CuC against human cancers in vitro and in viv...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01287
更新日期:2019-11-08 00:00:00
abstract::Cervical cancer is the fourth most common cancer that affects women, mainly through human papilloma virus (HPV) infection with high-risk HPV16 and HPV18. The present study investigated the in vitro anticancer activity and mechanism of action of a proanthocyanidin polymer-rich fraction of Stryphnodendron adstringens (F...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00694
更新日期:2018-07-03 00:00:00
abstract::Gene targeting strategies have become a powerful technology for elucidating mammalian gene function. The recently generated knockout (KO)-first strategy produces a KO at the RNA processing level and also allows for the generation of conditional KO alleles by combining FLP/FRT and Cre/loxP systems, thereby providing hi...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2013.00061
更新日期:2013-05-09 00:00:00
abstract::Bangpungtongsung-san (BTS) is a traditional Korean medicine consisting of 18 herbs, some which have antidepressant effects. Here, we used an animal model of reserpine-induced depression and lipopolysaccharide (LPS)-stimulated BV2 microglia to assess the antidepressant and anti-neuroinflammatory effects of BTS. Aside f...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00958
更新日期:2020-07-10 00:00:00
abstract::Free radicals act as secondary messengers, modulating a number of important biological processes, including gene expression, ion mobilization in transport systems, protein interactions and enzymatic functions, cell growth, cell cycle, redox homeostasis, among others. In the cardiovascular system, the physiological gen...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00382
更新日期:2019-04-12 00:00:00
abstract::Human peripheral-blood monocytes are used as an established in vitro system for generating macrophages. For several reasons, monocytic cell lines such as THP-1 have been considered as a possible alternative. In view of their distinct developmental origins and phenotypic attributes, we set out to assess the extent to w...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00071
更新日期:2018-02-22 00:00:00
abstract::Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase recently implicated in biochemical, physiological, and behavioral responses to ethanol. Thus, manipulation of ALK signaling may represent a novel approach to treating alcohol use disorder (AUD). Ethanol induces adaptations in glutamatergic synapses onto nu...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00533
更新日期:2017-08-15 00:00:00
abstract::[This retracts the article on p. 15 in vol. 2, PMID: 21687510.]. ...
journal_title:Frontiers in pharmacology
pub_type: 撤回出版物
doi:10.3389/fphar.2014.00283
更新日期:2014-12-17 00:00:00
abstract::Agrocybe aegerita has long been utilized for promoting diuresis in traditional Chinese medicine (TCM) with a close correlation to hypouricemia. Ethanol (AAE) and water (AAW) extracts of the compound led to a remarkable decrease in serum uric acid levels (SUA) in hyperuricemia mice, approaching that of the normal contr...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00498
更新日期:2018-05-15 00:00:00
abstract::Cognitive impairment is a central feature of schizophrenia and has shown to play a crucial role in the psychosocial function of the disorder. Over the past few years, several cognitive remediation (CR) interventions have been developed for schizophrenia, whose effectiveness has also been widely demonstrated by systema...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.01542
更新日期:2019-01-10 00:00:00
abstract::Background: Inhibiting proliferation and inducing apoptosis of myofibroblasts is becoming one of the promising and effective ways to treat hypertrophic scar. ABT-263, as an orally bioavailable BCL-2 family inhibitor, has showed great antitumor characteristics by targeting tumor cell apoptosis. The objective of this st...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.615505
更新日期:2021-01-14 00:00:00
abstract::Glucocorticoids (GCs) are the most commonly used drugs for treatment of autoimmune and inflammatory diseases. Their efficacy is due to their ability to bind cytoplasmic receptors (glucocorticoid receptors, GR) and other cytoplasmic proteins, thus regulating gene expression. Although GCs are potent life-saving drugs, t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00308
更新日期:2019-03-27 00:00:00
abstract::In iron overload disorders a significant fraction of the total iron circulates in the plasma as low molecular weight complexes not bound to transferrin, known as non-transferrin-bound iron (NTBI). By catalyzing the formation of free radicals, NTBI accumulation results in oxidative stress and cellular damage, being a m...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2014.00024
更新日期:2014-02-26 00:00:00
abstract:Introduction:Practical adherence barriers (e.g., medication frequency) are generally more amenable to intervention than perceptual barriers (e.g., beliefs). Measures which assess adherence barriers exist, however these tend to measure a mix of factors. There is a need to identify what practical barriers are captured by...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00572
更新日期:2020-05-13 00:00:00
abstract::Background and Objective: Idiopathic central precocious puberty (ICPP) is characterized by early pubertal changes, the acceleration of growth velocity, and rapid bone maturation that often results in reduced adult height. Gonadotrophin-releasing hormone agonist (GnRHa) is currently considered to be an effective therap...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00104
更新日期:2019-02-11 00:00:00
abstract::Various isoforms of myocyte enhancer factor 2 (MEF2) have been shown to play a role in the activation of rat hepatic stellate cells (HSCs) in culture. The signals that regulate MEF2 in HSCs are unknown. In addition, whether MEF2s regulate the activation of human HSCs (H-HSCs) is unclear. Here, we studied the expressio...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00322
更新日期:2019-04-11 00:00:00