Abstract：
:Inhaled corticosteroids (ICS) are recommended treatments for all degrees of asthma severity and in combination with bronchodilators are indicated for COPD patients with a history of frequent exacerbations. However, the long-term side effects of glucocorticoids (GCs) may include increased risk of respiratory infections, including viral triggered exacerbations. Rhinovirus (RV) infection is the main trigger of asthma and COPD exacerbations. Thus, we sought to explore the influence of GCs on viral replication. We demonstrate the ICS fluticasone propionate (FP) and two selective non-steroidal (GRT7) and steroidal (GRT10) glucocorticoid receptor (GR) agonists significantly suppress pro-inflammatory (IL-6 and IL-8) and antiviral (IFN-λ1) cytokine production and the expression of the interferon-stimulated genes (ISGs) OAS and viperin in RV-infected bronchial epithelial cells, with a consequent increase of viral replication. We also show that FP, GRT7 and GRT10 inhibit STAT1 Y701 and/or STAT2 Y690 phosphorylation and ISG mRNA induction following cell stimulation with recombinant IFN-β. In addition, we investigated the effects of the ICS budesonide (BD) and the long-acting β2 agonist (LABA) formoterol, alone or as an ICS/LABA combination, on RV-induced ISG expression and viral replication. Combination of BD/formoterol increases the suppression of OAS and viperin mRNA observed with both BD and formoterol alone, but an increase in viral RNA was only observed with BD treatment and not with formoterol. Overall, we provide evidence of an impairment of the innate antiviral immune response by GC therapy and the potential for GCs to enhance viral replication. These findings could have important clinical implications.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Marcellini A,Swieboda D,Guedán A,Farrow SN,Casolari P,Contoli M,Johnston SL,Papi A,Solari Rdoi
10.1016/j.ejphar.2020.173839subject
Has Abstractpub_date
2021-02-15 00:00:00pages
173839eissn
0014-2999issn
1879-0712pii
S0014-2999(20)30944-4journal_volume
893pub_type
杂志文章abstract：:A prohormone angiotensin antagonist, Sarcosyl1-Alanyl8-angiotensin I (Sar1-Ala8-A-I) was synthesized and its pharmacological properties were evaluated in three biological systems. It was found to be a good inhibitor in vivo in the rat blood pressure assay, somewhat less active in guinea pig ileum and a relatively weak...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90421-7
更新日期：1979-02-15 00:00:00
abstract：:The insulin secretagogue activity of certain imidazoline compounds is mediated by a binding site associated with ATP-sensitive K+ (K(ATP)) channels in the pancreatic beta-cell. We describe the effects of a series of structural modifications to efaroxan on its activity at this site. Substitution of amino-, nitro- or az...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00466-x
更新日期：1998-08-14 00:00:00
abstract：:Clozapine, an atypical neuroleptic drug devoid of extrapyramidal side effects, was a moderately potent, competitive inhibitor of the binding of [3H]quaternised ICS 205-930 to 5-HT3 receptor sites in rat cortical membranes, possessing a pKi value of 7.0. In contrast, several other antipsychotic agents, including fluphe...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90043-6
更新日期：1990-07-17 00:00:00
abstract：:When the prostate cancer cells become unresponsive to androgen therapy, resistance to chemotherapy becomes imminent, resulting in high mortality. To combat this situation, lycopodine, a pharmacologically important bioactive component derived from Lycopodium clavatum spores, was tested against hormone sensitive (LnCaP)...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.10.041
更新日期：2013-01-05 00:00:00
abstract：:The action of (+)-S-12967 and (-)-S-12968, two isomers of a new 1,4-dihydropyridine molecule (2-(-7-amino-2,5-dioxaheptyl)-3-ethoxycarbonyl-4-(2,3-dichlorop hen yl)-5-methoxycarbonyl-6-methyl 1,4-dihydropyridine), was studied on responses of rat isolated coronary resistance arteries (i.d. about 230 microns) to K+, Ca...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90501-8
更新日期：1993-07-06 00:00:00
abstract：:Preeclampsia is reported in pregnant women around the world and often causes maternal/fetal mortality and morbidity. In the current study, we assessed the efficacy of celastrol on a rat preeclampsia model induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). Pregnant rats were administered L-NAME to esta...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2018.04.025
更新日期：2018-07-05 00:00:00
abstract：:Cyclosporin A is shown to attenuate antinociceptive effects of morphine, development and expression of morphine-induced tolerance and dependency via nitric oxide (NO) pathway. In the present study, the effect of systemic cyclosporin A on morphine-induced conditioned place preference (CPP) and the probable involvement ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.11.025
更新日期：2005-01-10 00:00:00
abstract：:Sensitization to the discriminative stimulus effects of psychostimulants is not fully understood. Therefore, the present study was designed to investigate the development of sensitization to the discriminative stimulus of methamphetamine in rats. A dose-response curve for methamphetamine and a generalization test for ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.07.064
更新日期：2004-09-13 00:00:00
abstract：:The receptor for gonadotropin-releasing hormone (GnRH) belongs to the G-protein-coupled receptors, and its stimulation activates extracellular signal-regulated protein kinase (ERK). In the present study, we first examined the actions of GnRH on the ErbB family using two types of cultured gonadotroph cells. As reported...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.02.006
更新日期：2017-03-15 00:00:00
abstract：:Naloxone, a competitive antagonist of opioid receptors, and placebo (dextrose 5% in water (D5W) were administered on separate days to healthy normotensive (NT) male volunteers and to male patients with essential hypertension (HT). A single-blind, placebo-controlled, cross-over design was employed. Increasing doses of ...
journal_title：European journal of pharmacology
pub_type： 临床试验,杂志文章
doi：10.1016/0014-2999(86)90048-8
更新日期：1986-07-31 00:00:00
abstract：:The effects of bepridil and nifedipine, newly developed Ca2+ antagonists, were studied on the spontaneous action potentials of the true pacemaker cell preparations (0.5 X 0.5 mm) obtained from the rabbit sino-atrial (SA) node. At the lower concentrations, bepridil (10(-6) M) and nifedipine (10(-8) M) decreased the spo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90245-0
更新日期：1984-03-23 00:00:00
abstract：:2-n-Butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl-4-yl)methyl]imidazole, potassium salt (Losartan) (previous name, DuP 753 or MK 954) is a nonpeptide angiotensin II receptor antagonist. This study was performed to investigate the ability of Losartan to inhibit the angiotensin II-induced stimulatio...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(92)90130-n
更新日期：1992-10-01 00:00:00
abstract：:A novel growth hormone secretagogues type 1a (GHS1a) receptors antagonist (2R)-N'-[3,5- bis(trifluoromethyl)phenyl]-2-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-2-(3- pyridinyl)ethanohydrazide (GSK1614343) was functionally characterised in rat pituitary adenoma cell line, RC-4B/C endogenously expressing GHS1a rec...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.10.042
更新日期：2011-01-10 00:00:00
abstract：:The present study was designed to characterize the vasopressin receptor subtype involved in the vasopressin-induced activation of the central sympatho-adrenomedullary outflow using urethane-anesthetized rats. Intracerebroventricularly (i.c.v.) administered vasopressin (0.1, 0.2 and 0.5 nmol/animal) dose-dependently el...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)02652-3
更新日期：2002-12-13 00:00:00
abstract：:Peripheral nerve injury, which gives rise to persistent chronic pain, has become an area of intense research activity, largely because it represents a disorder with a high unmet medical need. In this study, serum biomarkers of the spinal nerve ligation model were successfully investigated with the metabolomic method. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.03.079
更新日期：2009-08-01 00:00:00
abstract：:Pulmonary arterial remodeling is a crucial cause of increased pulmonary artery pressure during pulmonary hypertension (PH). Recently, growing evidence has upheld the contribution of endothelial-mesenchymal transition (EndMT) to pulmonary arterial remodeling, but the underlying mechanisms remain largely unaddressed. mi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2019.172673
更新日期：2019-11-15 00:00:00
abstract：:Human adipose tissue-derived stromal cells (hADSCs) demonstrate promising potential in various clinical applications, including the transplantation to regenerate injured or degenerative tissues. The migration of engrafted hADSCs to the correct site of injure is essential for the curative effect of stem cell therapy. W...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.09.030
更新日期：2008-12-03 00:00:00
abstract：:Recombinant vaccinia viruses harboring the human dopamine D4 receptor cDNA containing two 48 base pair-repeats (D4.2) or the rat dopamine D2 short (D2s) receptor cDNA were used to infect rat-1 fibroblasts. Heterologous expression of both dopamine receptors was demonstrated in binding assays. The affinity constants of ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(95)90011-x
更新日期：1995-06-23 00:00:00
abstract：:Colorectal cancer (CRC) has become one of the major factors of tumor-related morbidity and mortality in the world because of its poor prognosis and consequences of metastatic spread. Currently, chemoprevention has been considered as a way of preventing cancer who takes advantage of plant phytochemicals and synthetic c...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2020.173588
更新日期：2020-11-15 00:00:00
abstract：:Previous results show that prolonged treatment with EMD-87580 (EMD) NHE-1 blocker attenuates and reverses postinfarction remodelling. Our aim was to evaluate the effects of the treatment of EMD compared to ischemic postconditioning (IPO) in a model of regional ischemia. Isolated hearts were subjected to 40-min coronar...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.05.010
更新日期：2014-08-15 00:00:00
abstract：:As part of a program aimed at designing irreversible antagonists of the stimulant and reinforcing properties of cocaine, derivatives of GBR-12783 containing electrophilic substituents were synthesized. GBR-12783, a potent and selective inhibitor of both stimulant binding and dopamine transport, was modified to incorpo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90745-p
更新日期：1992-09-22 00:00:00
abstract：:This study shows that in spontaneously hypertensive rats (SHR) of 14-weeks-old, the sympathetically-induced, but not noradrenaline-induced tachycardic response are higher than age-matched Wistar normotensive rats. Furthermore, in SHR the sympathetically-induced tachycardic response was: (1) unaffected by moxonidine (3...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.08.017
更新日期：2016-11-15 00:00:00
abstract：:meta-Substituted 2-chlorophenyl(imino)imidazolidines of the clonidine-type (2,3- and 2,5-substituted derivatives) were used in attempts to discriminate between alpha-adrenergic effects (central hypotensive and peripheral hypertensive activities) in rats. The central hypotensive activity of four pairs of substitution i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90185-0
更新日期：1981-05-22 00:00:00
abstract：:Endogenous opioid and nociceptin systems are widely distributed in the gastrointestinal tract where they seem to play a crucial role in maintaining the intestinal homeostasis. The aim of our study was to assess whether activation of nociceptin (NOP) and µ-opioid (MOP) receptors by a mixed NOP/MOP receptor agonist, BU0...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.09.021
更新日期：2015-10-15 00:00:00
abstract：:In type 1 diabetes, there is a rapid loss of glycemic control immediately after onset of the disease. We aimed to determine if the deterioration of glycemic control that occurs early after the onset of insulin-deficient diabetes could be blunted by treatment with recombinant fibroblast growth factor 21 (FGF21). Normal...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.07.003
更新日期：2015-10-05 00:00:00
abstract：:Some studies have suggested that drug tolerance observed following repeated benzodiazepine exposure may be associated with the development of a subsensitivity to gamma-aminobutyric acid (GABA) in dorsal raphe and hippocampal neurons. In other areas such as the substantia nigra such subsensitivity has not been found. T...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00053-2
更新日期：1996-04-22 00:00:00
abstract：:Modafinil [2-((diphenylmethyl) sulfinyl) acetamide] is a central nervous system stimulant. It has received considerable attention as a potential psychotropic agent in several psychiatric disorders. The current study was carried out to investigate the effect of modafinil after acute administration on animal models of p...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.04.035
更新日期：2014-08-05 00:00:00
abstract：:Grooming behaviour in mice was dose dependently increased by SK&F 38393 (1.87-30 mg/kg), whereas it was dose dependently decreased by RU 24926 (2.5-10 mg/kg) or LY 171555 (0.4-1.6 mg/kg) alone or combined with SK&F 38393 or apomorphine (0.39-6 mg/kg). The inhibitory effect of 0.75 mg/kg apomorphine on grooming behavio...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90141-0
更新日期：1988-10-26 00:00:00
abstract：:Barbiturates and the related depressant drugs, etazolate and etomidate, inhibited both the binding of [3H]bicuculline methochloride (BMC) to gamma-aminobutyric acid (GABA) receptor sites and the binding of [3H] beta-carboline-3-carboxylic acid methyl ester (beta CCM) to benzodiazepine receptor sites in mammalian brain...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90252-8
更新日期：1984-07-13 00:00:00
abstract：:To investigate the structure-activity relationships for potent and selective action of enkephalins at the delta-opioid receptors, two newly synthesized analogues, [Cys(O2NH2)2,Leu5]enkephalin and [Cys(O2NH2)2, Met5] enkephalin and the hexapeptide [D-Ala2,Leu5]enkephalyl-Arg (dalargin) were tested and compared with [Le...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00083-0
更新日期：1996-05-23 00:00:00
