Abstract:
:Asthma is an inflammatory disease of the lungs and the transcription factor NF-kappa B regulates the production of numerous inflammatory mediators that may have a role in the pathogenesis of asthma. Hence, the signalling pathways leading to NF-kappa B activation are considered prime targets for novel anti-inflammatory therapies. The prevention of NF-kappa B activity in mice, through the knockout of IKK beta or p65, causes fatal liver degeneration in utero making it difficult to determine the full implications of inhibiting NF-kappaB activity in tissues physiologically relevant to human diseases. This study used adenovirus delivery of a dominant inhibitor of NF-kappaB (I kappa B alpha delta N) and dominant-negative IKK alpha (IKK alpha(KM)) and IKK beta (IKK beta(KA)) to investigate the role of the individual IKKs in NF-kappa B activation and inflammatory gene transcription by human pulmonary A549 cells. Overexpression of IKK beta(KA) or I kappa B alpha delta N prevented NF-kappa B-dependent transcription and DNA binding. IKK beta(KA) also prevented I kappa B alpha kinase activity. Similarly, IKK beta(KA) and I kappa B alpha delta N overexpression also inhibited IL-1beta- and TNF alpha-dependent increases in ICAM-1, IL-8 and GM-CSF in addition to IL-1beta-mediated increases in cyclooxygenase-2 expression, whereas IKK alpha(KM) overexpression had little effect on these outputs. IKK beta(KA) also reduced cell viability and induced caspase-3 and PARP cleavage regardless of the stimuli, indicating the induction of apoptosis. This effect seemed to be directly related to IKK beta kinase activity since I kappa B alpha delta N only induced PARP cleavage in TNF alpha-treated cells. These results demonstrate that inhibition of IKK beta and NF-kappa B suppresses inflammatory mediator production and reduces A549 cell viability. Thus, novel therapies that target IKK beta could have potent anti-inflammatory effects and may be beneficial in the treatment of certain cancers.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Catley MC,Chivers JE,Holden NS,Barnes PJ,Newton Rdoi
10.1038/sj.bjp.0706170subject
Has Abstractpub_date
2005-05-01 00:00:00pages
114-22issue
1eissn
0007-1188issn
1476-5381pii
0706170journal_volume
145pub_type
杂志文章abstract::1. The purpose of this investigation was to examine the outputs of peptide histidine isoleucine (PHI) and vasoactive intestinal peptide (VIP) from the gastric corpus in response to stimulation of the peripheral (PVS) and central (CVS) ends of the vagus nerve and to compare the effects of PHI on gastric motility and bl...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb15787.x
更新日期:1990-06-01 00:00:00
abstract::S-nitrosothiols have a number of potential clinical applications, among which their use as antithrombotic agents has been emphasized. This is largely because of their well-documented platelet inhibitory effects, which show a degree of platelet selectivity, although the mechanism of this remains undefined. Recent progr...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2010.00670.x
更新日期:2010-04-01 00:00:00
abstract::The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine on compound action potentials were investigated in de-sheathed frog-sciatic nerve preparations. ATP and ADP but not adenosine antagonized the inhibitory action of tetrodotoxin (TTX) on nerve conductio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10075.x
更新日期:1984-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, right ventricular hypertrophy and increased right ventricular systolic pressure. Here, we investigated the effects of a N-acylhydrazone derivative, 3,4-dimethoxyphenyl-N-methyl-benzoylhydrazide (LASS...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12193
更新日期:2013-07-01 00:00:00
abstract::1. Adenosine A(1), A(2A), and A(3) receptors (ARs) and extracellular signal-regulated kinase 1/2 (ERK1/2) play a major role in myocardium protection from ischaemic injury. In this study, we have characterized the adenosine receptor subtypes involved in ERK1/2 activation in newborn rat cardiomyocytes. 2. Adenosine (non...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705614
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Carboxylesterases (CEs) metabolize a wide range of xenobiotic substrates including heroin, cocaine, meperidine and the anticancer agent CPT-11. In this study, we have purified to homogeneity human liver and intestinal CEs and compared their ability with hydrolyse heroin, cocaine and CPT-11. EXPE...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00700.x
更新日期:2010-08-01 00:00:00
abstract::Analogues of gamma-aminobutyric acid (GABA) incorporating an isothiouronium salt as a replacement for a protonated amino functional group have been investigated for activity on: GABA receptors in the guinea-pig ileum; [3H]-GABA and [3H]-diazepam binding to rat brain membranes; and GABA uptake and transamination. For t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10214.x
更新日期:1986-06-01 00:00:00
abstract::1 Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) differentially activate three Y receptors (Y(1), Y(2) and Y(4)) in mouse and human isolated colon. 2 The aim of this study was to characterise Y(2) receptor-mediated responses in colon mucosa and longitudinal smooth muscle preparations from wild ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705298
更新日期:2003-06-01 00:00:00
abstract::1. The aim of this study was to characterize the tachykinin NK2 receptor subtype mediating the spasmogenic response in the human isolated bronchus. The motor response to neurokinin A (NKA) and the selective NK2 agonist [beta Ala8]NKA(4-10), as well as the antagonistic effects of cyclic (L659,877) and linear (MEN 10376...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14775.x
更新日期:1994-02-01 00:00:00
abstract::Optimum assay conditions for the association of [3H]-para-tyramine [( 3H]-pTA) with rat brain membranes were characterized, and a saturable, reversible, drug-specific, and high affinity binding mechanism for this trace amine was revealed. The binding capacity (Bmax) for [3H]-pTA in the corpus striatum was approximatel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb11116.x
更新日期:1986-09-01 00:00:00
abstract::1. The intravenous, subcutaneous and oral toxicity of ambenoxan in mice is reported.2. Ambenoxan is a centrally acting skeletal muscle relaxant shown to be effective in mice, rats, rabbits, dogs and monkeys without loss of the righting reflex.3. It had no peripheral neuromuscular blocking properties.4. Decerebrate rig...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb08515.x
更新日期:1970-02-01 00:00:00
abstract::1. The effects of intracameral injections of prostaglandins E(1), E(2), F(1a), F(2a), and A(1) were studied on the intraocular pressure (IOP) of rabbits anaesthetized with urethane.2. With the exception of prostaglandin F(1a), all the prostaglandins studied were found to be capable of producing a large, sustained rise...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb09533.x
更新日期:1969-09-01 00:00:00
abstract::1. The effects of pinacidil on noradrenaline-induced tone, smooth muscle membrane potential and 42K- and 86Rb-efflux from isolated mesenteric resistance vessels (internal diameter 200 microns) of the rat have been studied. 2. Pinacidil (0.3-10 microM) produced concentration-dependent suppression of noradrenaline-induc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb16553.x
更新日期:1988-09-01 00:00:00
abstract::1. The cardiovascular and behavioural effects elicted by the intracerebroventricular (i.c.v.) injection of substance P (SP), neurokinin A (NKA), [MePhe7]neurokinin B ([MePhe7]NKB) or angiotensin II (AII) in the conscious rat were assessed before and 5 min after i.c.v. pretreatment with antagonists selective for angiot...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb14940.x
更新日期:1995-04-01 00:00:00
abstract::1 The effects of diltiazem on smooth muscle cells of the canine basilar artery were investigated by means of microelectrode, double sucrose gap and isometric tension recording methods. 2 The mean membrane potential of the smooth muscle cells was -49.8 mV and they were electrically quiescent. Diltiazem (over 10(-5) M) ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09162.x
更新日期:1982-03-01 00:00:00
abstract::The above article, published by the British Journal of Pharmacology in October 2015 (https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.13259), has been retracted by agreement between the authors, the journal Editor in Chief and John Wiley & Sons Limited. The retraction has been agreed owing to the discovery...
journal_title:British journal of pharmacology
pub_type: 杂志文章,撤回出版物
doi:10.1111/bph.14349
更新日期:2018-07-01 00:00:00
abstract::1. Acetylcholine mustard (N-2-chloroethyl-N-methyl-2-acetoxyethylamine), a potent muscarinic agonist, binds virtually irreversibly to muscarinic receptors in longitudinal muscle strips from guinea-pig small intesting, as shown by the inhibition of the binding of E13-H]-propylbenzilycholine mustard ([3-H-PrBCM), an aff...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07372.x
更新日期:1975-03-01 00:00:00
abstract::Gene silencing techniques are gaining increasing popularity in the literature, both as a tool for unravelling gene function and to potentially deliver therapeutic benefit, especially in the context of cardiovascular disease. Gene-specific catalytic DNA molecules, or DNAzymes, have shown promise in ameliorating the eff...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/bjp.2008.145
更新日期:2008-06-01 00:00:00
abstract::1. The effects of seven agonist and three antagonist adenosine receptor ligands were compared on the guinea-pig sinoatrial (SA) node (isolated right atrium) and atrioventricular (AV) node (perfused whole heart). Single agonist concentration-effect curves were obtained to 5'-N-ethylcarboxamidoadenosine (NECA), R(-)-N6-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701891
更新日期:1998-06-01 00:00:00
abstract::1. The possible mechanisms of action of the inhibitory effect of gomisin C on the respiratory burst of rat neutrophils in vitro was investigated. 2. The peptide formyl-Met-Leu-Phe (FMLP) induced superoxide anion (O2-) formation and O2 consumption, which was inhibited by gomisin C in a concentration-dependent manner (I...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17084.x
更新日期:1994-11-01 00:00:00
abstract::1. The action of substance P (SP) on the release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) and on contraction were studied in strips of the guinea-pig urinary bladder. Substance P induced a dose-dependent contraction of strips of guinea-pig urinary bladder (EC50 = 1.2 x 10(-9) M). This contraction was ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12615.x
更新日期:1989-10-01 00:00:00
abstract::There are proposals for the implementation of beta(2)-adrenoceptor agonists for the management of muscle wasting diseases. The idea has been initiated by studies in animal models which show that beta(2)-adrenoceptor agonists cause hypertrophy of skeletal muscle. Their use in clinical practice will also need an underst...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706670
更新日期:2006-03-01 00:00:00
abstract::1. The purpose of the present investigations was to determine the influence of increasing age on the pharmacokinetics and pharmacodynamics of midazolam in male BN/BiRij rats as an animal model of aging. 2. Midazolam was administered intravenously at a dose of 2.5 mg kg-1 and its pharmacokinetics were determined on the...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14482.x
更新日期:1992-09-01 00:00:00
abstract::1 The actions of ethylenediamine (EDA) and structurally related compounds were investigated by microiontophoresis in Wistar rats. 2 EDA inhibited, via a bicuculline-sensitive mechanism, the spontaneous firing rate of all cortical and pallidal cells tested. 3 The results with the analogues suggest that two amine groups...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08761.x
更新日期:1982-01-01 00:00:00
abstract::The endothelial 5-HT receptor mediating relaxation of pig pulmonary artery has been characterized using the selective 5-HT(2B) receptor agonist BW 723C86 and a variety of structurally diverse 5-HT receptor antagonists. If arterial rings with intact endothelium were precontracted with prostaglandin F(2alpha) (3 microM)...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703341
更新日期:2000-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Intrathecal administration of alpha(2)-adrenoceptor agonists produces potent analgesia. This study addressed the subtype of spinal alpha(2)-adrenoceptor responsible for the analgesic effects of i.t. dexmedetomidine and ST-91 in the formalin behavioural model and their effects on primary afferent ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.341
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Red wine polyphenols (RWPs) inhibit the expression of vascular endothelial growth factor (VEGF), a major pro-angiogenic and pro-atherosclerotic factor, in vascular smooth muscle cells (VSMCs). The aim of this study was to identify which red wine polyphenols were inhibitory and to determine the me...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706843
更新日期:2006-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.01179.x
更新日期:2011-04-01 00:00:00
abstract::1. Effects of morphine sulphate (1.25, 2.5, 5, 10, 20 and 40 mg/kg i.p.) on locomotor activity of male rats were observed for 8 h after single doses in non-tolerant rats. The lower three doses had only an excitatory effect, whereas the higher three doses caused initial depression followed by a delayed excitatory effec...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb06866.x
更新日期:1972-10-01 00:00:00
abstract::The effects of treatment with rolipram, a specific phosphodiesterase IV inhibitor, on learning and memory function and on the cyclic AMP/PKA/CREB signal transduction system were examined in rats with microsphere embolism (ME)-induced cerebral ischaemia. Sustained cerebral ischaemia was induced by the injection of 900 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704629
更新日期:2002-04-01 00:00:00