Abstract:
:Airway smooth muscle (ASM) cells can act as effector cells in the initiation and/or perpetuation of airway inflammation in asthma by producing various inflammatory chemokines or cytokines. Previous studies from our laboratory and others showed that the combination of tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) or endogenous IFNbeta results in a synergistic induction of various pro-inflammatory genes, including CD38 and regulated upon activation normal T-cell expressed and secreted (RANTES), in ASM cells. In contrast to these studies, we found that IFNgamma (1000 U/ml) markedly inhibited TNFalpha-induced expression of interleukin (IL)-6, IL-8, and eotaxin by 66.29+/-3.33, 43.86+/-7.11, and 63.25+/-6.46%, respectively. These genes were also found to be NF-kappaB-dependent in that TNFalpha-induced expression of IL-6, IL-8, and eotaxin was dose-dependently inhibited by the selective IKKbeta inhibitor 4-(2'-aminoethyl)amino-1,8-dimethylimidazo[1,2-a]quinoxaline (BMS-345541) (1-30 microM). Using a luciferase reporter construct containing kappaB sites, we found that IFNgamma (10-1000 U/ml) inhibits NF-kappaB-dependent gene transcription in a dose-dependent manner. Moreover, IFNgamma failed to affect TNFalpha-induced IkappaKbeta phosphorylation or IkappaB degradation as well as nuclear NF-kappaB/DNA interaction. It is noteworthy that IFNgamma decreases TNFalpha-induced histone acetyl transferase (HAT) and increases histone deacetylase (HDAC) activities. Finally, trichostatin A, an HDAC inhibitor, prevents IFNgamma inhibitory action on TNFalpha-induced gene expression. Together, our data indicate that IFNgamma is a potent inhibitor of specific TNFalpha-inducible inflammatory genes by acting on NF-kappaB transactivation via the modulation of HDAC function.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Keslacy S,Tliba O,Baidouri H,Amrani Ydoi
10.1124/mol.106.030171subject
Has Abstractpub_date
2007-02-01 00:00:00pages
609-18issue
2eissn
0026-895Xissn
1521-0111pii
mol.106.030171journal_volume
71pub_type
杂志文章abstract::The members of the Cys-loop ligand-gated ion channel (LGIC) gene family play a major role in fast synaptic transmission, and these receptors represent an important class of targets for therapeutic agents. Each member of this gene family is a pentameric complex containing one or more different subunits, and a large num...
journal_title:Molecular pharmacology
pub_type: 评论,杂志文章,评审
doi:10.1124/mol.105.020727
更新日期:2006-02-01 00:00:00
abstract::Retinoid X receptor α [RXRα; nuclear receptor (NR)2B1] is a crucial regulator in the expression of a broad array of hepatic genes under both normal and pathologic conditions. During inflammation, RXRα undergoes rapid post-translational modifications, including c-Jun N-terminal kinase (JNK)-mediated phosphorylation, wh...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.113.085555
更新日期:2013-08-01 00:00:00
abstract::The delta family of ionotropic glutamate receptors consists of glutamate delta-1 (GluD1) and glutamate delta-2 receptors. We have previously shown that GluD1 knockout mice exhibit features of developmental delay, including impaired spine pruning and switch in the N-methyl-D-aspartate receptor subunit, which are releva...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.104786
更新日期:2016-08-01 00:00:00
abstract::Quinones undergo redox cycling and/or arylation reactions with key biomolecules involved with cellular Ca2+ regulation. The present study utilizes nanomolar quantities of the fluorogenic maleimide 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM) to measure the reactivity of hyperreactive sulfhydryl moieti...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::Receptors from distant species may have conserved functions despite significant differences in protein sequences. Whereas the noncritical residues are often changed in distant species, the amino acids critical in receptor functions are often conserved. Studying the conserved residues between receptors from distant spe...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.111.074500
更新日期:2011-11-01 00:00:00
abstract::We examined the influence of the molecular structure of four novel adamantane derivatives on their ability to block the channels of nicotinic acetylcholine (ACh) and N-methyl-D-aspartate (NMDA) receptors. The structure of the drugs is Ad-CH2-N+H2-(CH2)5-R, where Ad is adamantane and R was varied from ammonium (IEM-175...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::Cyclic nucleotide phosphodiesterases (PDEs) from canine trachealis were characterized with respect to their kinetic properties, sensitivity to selective inhibitors, and subcellular distribution. Extracts from whole tissue homogenates were applied to DEAE-Sepharose anion exchange columns and eluted with a linear sodium...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::The bisdioxopiperazines such as (+)-(S)-4,4'-propylenedi-2,6-piperazinedione (dexrazoxane; ICRF-187), 1,2-bis(3,5-dioxopiperazin-1-yl)ethane (ICRF-154), and 4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione (ICRF-193) are agents that inhibit eukaryotic topoisomerase II, whereas their ring-opened hydrolysis pro...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.036970
更新日期:2007-10-01 00:00:00
abstract::GABAA receptors are modulated by a variety of compounds, including the neurosteroids and barbiturates. Although the effects of barbiturates on alphabetagamma isoforms, thought to dominate phasic (synaptic) GABAergic inhibition, have been extensively studied, the effects of pentobarbital on kinetic properties of alphab...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.002543
更新日期:2004-10-01 00:00:00
abstract::Dysfunction of p53 and resistance to cancer drugs can arise through mutually exclusive overexpression of MDM2 or MDM4. Cisplatin-resistant cells, however, can demonstrate increased binding of both MDM2 and MDM4 to p53 but in absence of cellular overexpression. Whether MDM2 inhibitors alone can activate p53 in these re...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.117564
更新日期:2020-04-01 00:00:00
abstract::Past decades of cancer research have mainly focused on the role of various extracellular and intracellular biochemical signals on cancer progression and metastasis. Recent studies suggest an important role of mechanical forces in regulating cellular behaviors. This review first provides an overview of the mechanobiolo...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.116.106765
更新日期:2016-12-01 00:00:00
abstract::A UDP-glucuronosyltransferase (UDPGT) isoenzyme capable of morphine glucuronidation has been purified to apparent homogeneity and partially characterized from hepatic microsomes of female Wistar rats which have low 3 alpha-hydroxysteroid UDPGT. A rapid and sensitive assay was developed to quantify morphine glucuronide...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-12-01 00:00:00
abstract::The ligand specificity of rat adenohypophyseal vasopressin receptors was directly compared to that of peripheral receptors of the V1 and V2 types. For this purpose a series of 15 recently designed vasopressin antagonists was used. The affinities of these antagonists for rat adenohypophyseal membranes were deduced from...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00
abstract::Iron is a biologically essential metal, but excess iron can cause damage to the cardiovascular and nervous systems. We examined the effects of extracellular Fe²⁺ on permeation and gating of Ca(V)3.1 channels stably transfected in HEK293 cells, by using whole-cell recording. Precautions were taken to maintain iron in t...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.080184
更新日期:2012-12-01 00:00:00
abstract::Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are members of the phospholipid growth factor family. A major limitation in the field to date has been a lack of receptor subtype-specific agonists and antagonists. Here, we report that dioctylglycerol pyrophosphate and dioctylphosphatidic acid are selectiv...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::Four piperazinoquinolone antibacterial drugs (norfloxacin, ciprofloxacin, enoxacin, and pipemidic acid), known to be gamma-aminobutyric acid (GABA) antagonists, fully reversed the inhibitory effect of GABA on [35S]t-butylbicyclophosphorothionate ([35S] TBPS) binding to rat brain membranes in vitro. Twelve indomethacin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::Resveratrol (RES), a natural plant polyphenol, has gained interest as a nontoxic chemopreventive agent capable of inducing tumor cell death in a variety of cancer types. However, the early molecular mechanisms of RES-induced apoptosis are not well defined. Using the human breast cancer cell lines MDA-MB-231 and MCF-7,...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.039040
更新日期:2007-12-01 00:00:00
abstract::Platelet-activating factor (PAF) receptor-coupled activation of phosphoinositide-specific phospholipase C (PLC) was studied in platelets that were made refractory, by short-term pretreatments, to either PAF or thrombin. Generation of [3H]inositol triphosphate ( [3H]IP3) was monitored specifically for this purpose. [3H...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::The immunosuppressive agent cyclosporine A has been shown to reverse multidrug resistance (MDR) in malignant cells. In the present study, a 3H-cyclosporine diazirine analogue was used to photolabel viable MDR Chinese hamster ovary cells. The 170-kDa membrane P-glycoprotein, which functions as a drug efflux pump, was s...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract::The chelator di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) shows potent and selective anticancer and antimetastatic activity. However, the mechanism by which it is initially transported into cells to induce cytotoxicity is unknown. Hence, the current investigation examined the cellular uptake of ¹⁴C-Dp4...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.113.088393
更新日期:2013-12-01 00:00:00
abstract::The anti-human immunodeficiency virus (-HIV) nucleoside analogs azidothymidine (AZT), dideoxycytidine (ddC), dideoxyinosine (ddl), dideoxydidehydrothymidine (D4T), and dideoxydidehydrocytidine (D4C) and the anticancer drug cytosine arabinoside (AraC) were compared for their effects on the mitochondrial DNA (mtDNA) con...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::The sulfoconjugation of tyrosyl residues is a widespread post-translational modification of biologically active proteins and peptides. The rat liver Golgi enzyme tyrosylprotein sulfotransferase has previously been shown to catalyze the transfer of a sulfate moiety from 5'-phosphoadenosine-3'-phosphosulfate to the synt...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract::Aldose reductase (AKR1B1) is a critical drug target because of its involvement in diabetic complications, inflammation, and tumorigenesis. However, to date, development of clinically useful inhibitors has been largely unsuccessful. Cyclopentenone prostaglandins (cyPGs) are reactive lipid mediators that bind covalently...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.100693
更新日期:2016-01-01 00:00:00
abstract::The diphosphoinositol polyphosphates ("inositol pyrophosphates") are a specialized subgroup of the inositol phosphate signaling family. This review proposes that many of the current data concerning the metabolic turnover and biological effects of the diphosphoinositol polyphosphates are linked by a common theme: these...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.109.055897
更新日期:2009-08-01 00:00:00
abstract::Studies were carried out to elucidate the mechanism whereby thyroid hormone (T3) induces NADPH:cytochrome P450 oxidoreductase (P450R) mRNA in rat liver in vivo. Northern blot analysis revealed that T3 treatment increases unspliced liver nuclear P450R RNA 4-fold within 8 h and that this induction precedes the induction...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.59.5.987
更新日期:2001-05-01 00:00:00
abstract::Structural changes in the macromolecular targets of pharmacological agents can result in alterations in the efficacy of these agents. In previous studies, we identified a variant structural form of thymidylate synthase (TS) that is associated with relative resistance to 5-fluoro-2'-deoxyuridine, in a human colonic tum...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::Type II DNA topoisomerases are targets of acridine drugs. Nine mutations conferring resistance to acridines were obtained by forced molecular evolution, using methyl N-(4'-(9-acridinylamino)-3-methoxy-phenyl) methane sulfonamide (mAMSA), methyl N-(4'-(9-acridinylamino)-2-methoxy-phenyl) carbamate hydrochloride (mAMCA)...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.106.032953
更新日期:2007-04-01 00:00:00
abstract::Cross-talk between G protein-coupled receptors and protein tyrosine kinases is well established, but the phenotypic consequences of these signaling interactions are not completely understood. To investigate the role of Src family kinases in mitogenic signaling by G protein-coupled receptors, we used genetic and pharma...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.010546
更新日期:2005-06-01 00:00:00
abstract::Recently, inositol hexakisphosphate (phytic acid) was shown to bind to photoreceptor arrestin and block its interaction with rhodopsin. Such an interaction might predict that inositol polyphosphates could alter G protein-coupled receptor desensitization. To investigate the possible roles of higher inositol polyphospha...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::The mechanism underlying the crosstalk between multiple G protein-coupled receptors remains poorly understood. We previously reported that prostaglandin E receptor EP1 facilitates dopamine D1 receptor signaling in striatal slices and promotes behavioral responses induced by D1 receptor agonists. Here, using human embr...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.113.087288
更新日期:2013-09-01 00:00:00