Abstract:
BACKGROUND AND PURPOSE:Haem oxygenase-1 (HO-1) is induced by thiazolidinediones including rosiglitazone and exerts anti-inflammatory effects in various models. However, the molecular mechanisms underlying rosiglitazone-induced HO-1 expression remain largely unknown in human pulmonary alveolar epithelial cells (HPAEpiCs). EXPERIMENTAL APPROACH:HO-1 expression was determined by real time-PCR, Western blotting and promoter reporter analyses. Signalling pathways were investigated using pharmacological inhibitors or specific siRNAs. Interactions between nuclear factor erythroid-2-related factor (Nrf2) and antioxidant response elements (ARE) binding site of the HO-1 promoter were investigated with chromatin immunoprecipitation assays. KEY RESULTS:Up-regulation of HO-1 in HPAEpiCs or in mice by rosiglitazone blunted ICAM-1 expression and monocyte adhesion to HPAEpiCs challenged with LPS. Rosiglitazone-induced HO-1 expression was significantly attenuated by NADPH oxidase (NOX) inhibitors (apocynin and diphenyleneiodonium) or ROS scavenger (N-acetyl cysteine). The involvement of NOX activity and ROS generation in rosiglitazone-induced HO-1 expression was confirmed by transfection with p47phox or NOX2 siRNA. Moreover, pretreatment with the inhibitors of c-Src (c-Srci II), proline-rich tyrosine kinase 2 (Pyk2) (PF431396), Akt (Akti VIII) or PPARγ (GW9662) and transfection with siRNA of c-Src, Pyk2, Akt or PPARγ abolished the rosiglitazone-induced HO-1 expression in HPAEpiCs. Subsequently, Nrf2 was activated by phosphorylation of c-Src, Pyk2 and Akt, which turned on transcription of HO-1 gene by binding to AREs binding site and enhancing ARE promoter activity. CONCLUSIONS AND IMPLICATIONS:Rosiglitazone induces HO-1 expression via either NOX/ROS/c-Src/Pyk2/Akt-dependent Nrf2 activation or PPARγ in HPAEpiCs and suppresses LPS-mediated inflammatory responses, suggesting that PPARγ agonists may be useful for protection against pulmonary inflammation.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Cho RL,Yang CC,Tseng HC,Hsiao LD,Lin CC,Yang CMdoi
10.1111/bph.14465subject
Has Abstractpub_date
2018-10-01 00:00:00pages
3928-3946issue
20eissn
0007-1188issn
1476-5381journal_volume
175pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Up-regulation of thioredoxin interacting protein (TXNIP), an endogenous inhibitor of thioredoxin (Trx), compromises cellular antioxidant and anti-apoptotic defences and stimulates pro-inflammatory cytokines expression, implying a role for TXNIP in apoptosis. Here we have examined the causal role ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01336.x
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Although botulinum toxin type A (BoNT/A) is approved for chronic migraine treatment, its mechanism of action is still unknown. Dural neurogenic inflammation (DNI) commonly used to investigate migraine pathophysiology can be evoked by trigeminal pain. Here, we investigated the reactivity of crania...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13366
更新日期:2016-01-01 00:00:00
abstract::(1) Stimulation of the vanilloid receptor-1 (TRPV1) results in the activation of nociceptive and neurogenic inflammatory responses. Poor specificity and potency of TRPV1 antagonists has, however, limited the clarification of the physiological role of TRPV1. (2) Recently, iodo-resiniferatoxin (I-RTX) has been reported ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705110
更新日期:2003-03-01 00:00:00
abstract::1 The activation of tachykinin NK(1) receptors in the rat spinal cord produced a transient drop in arterial blood pressure followed by a more prolonged pressor effect which is mediated by the stimulation of the sympatho-adrenal system. This study aims at characterizing the spinal mechanism of that initial hypotension ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704813
更新日期:2002-08-01 00:00:00
abstract::Tyrosine sulfation is a post-translational modification of secreted and transmembrane proteins, including many GPCRs such as chemokine receptors. Most chemokine receptors contain several potentially sulfated tyrosine residues in their extracellular N-terminal regions, the initial binding site for chemokine ligands. Su...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12455
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:A functional link between seizure-induced P-glycoprotein overexpression at the blood-brain barrier and therapeutic failure has been suggested by several studies using rodent epilepsy models and human epileptic tissue. Recently, we reported that interference with the mechanisms that up-regulate P-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00765.x
更新日期:2010-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Down's syndrome is a common genetic cause of intellectual disability, for which there are no drug therapies. Mechanistic studies in a model of Down's syndrome [Ts65Dn (TS) mice] demonstrated that impaired cognitive function was due to excessive neuronal inhibitory tone. These deficits were normal...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12169
更新日期:2013-07-01 00:00:00
abstract::1. Arachidonic acid caused larger contractions to indomethacin-tested guinea-pig trachea than in control tracheae. 2. No change in contractions was obtained in tracheae treated with 5,8, 11, 14, eicosatetraynoic acid (ETYA 10 micro M). 3. ETYA (100 micro M) blocked the effect of indomethacin on arachidonic acid-induce...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09250.x
更新日期:1982-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The renal sodium-glucose cotransporter 2 (SGLT2) plays an important role in the reuptake of filtered glucose in the proximal tubule and therefore may be an attractive target for the treatment of diabetes mellitus. This study characterizes the pharmacological profile of TS-071 ((1S)-1,5-anhydro-1-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01340.x
更新日期:2011-09-01 00:00:00
abstract::1. The ability of memantine (1-amino-3,5-dimethyladamantane) to antagonize the modulatory effects of N-methyl-D-aspartate (NMDA) on phosphoinositide turnover stimulated by muscarinic cholinoceptor- and metabotropic glutamate receptor-agonists has been examined in neonatal rat cerebral cortex slices. 2. Memantine antag...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13275.x
更新日期:1995-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Δ9 -tetrahydrocannabinol (THC) acts via cannabinoid CB1 receptors to increase feeding. Here, we assessed the orexigenic effect of AM11101, a novel CB1 receptor agonist designed to have a more favourable pharmacodynamic profile than THC. EXPERIMENTAL APPROACH:The acute, orexigenic effects of AM11...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14797
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:N-arachidonoyl-serotonin (AA-5-HT) is an inhibitor of fatty acid amide hydrolase (FAAH)-catalysed hydrolysis of the endocannabinoid/ endovanilloid compound, anandamide (AEA). We investigated if AA-5-HT antagonizes the transient receptor potential vanilloid-1 (TRPV1) channel and, as FAAH and TRPV1...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707145
更新日期:2007-03-01 00:00:00
abstract::HMG-CoA reductase inhibitors (statins) have now become one of the most powerful pharmacological strategies in the treatment of cardiovascular diseases. Originally, the cardioprotective effects of statins were thought to be mediated through lipid lowering actions. However, it has now become increasingly clear that the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706863
更新日期:2006-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Immunomodulatory tetracyclines are well-characterized drugs with a pharmacological potential beyond their antibiotic properties. Specifically, minocycline and doxycycline have shown beneficial effects in experimental colitis, although pro-inflammatory actions have also been described in macrophag...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14494
更新日期:2018-12-01 00:00:00
abstract::1. DL-1-(2-acetyl-4-n-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropane hydrochloride (M & B 17803A) was given to four healthy volunteers in single oral doses of up to 300 mg. There were no subjective effects and no significant alterations in the heart rate, systolic and diastolic blood pressure in the seated posit...
journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1476-5381.1971.tb07193.x
更新日期:1971-11-01 00:00:00
abstract::1. The convulsive effects of leptazol in the rat are potentiated by prior treatment with dexamphetamine.2. An intact dopamine synthesis is necessary for the potentiation of the convulsive action of leptazol.3. An intact noradrenaline synthesis is not necessary for this action of amphetamine, as long as the dopamine sy...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb09526.x
更新日期:1969-09-01 00:00:00
abstract::1. Chronic treatment with a combined ETA/ETB endothelin receptor antagonist has been shown to reduce blood pressure in experimental rat models of hypertension in which endothelin-1 gene overexpression occurs in the walls of blood vessels, particularly small, resistance-sized arteries, but not in those genetic or exper...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701224
更新日期:1997-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The passage of drugs across the blood-brain barrier (BBB) limits the efficacy of chemotherapy in brain tumours. For instance, the anticancer drug doxorubicin, which is effective against glioblastoma in vitro, has poor efficacy in vivo, because it is extruded by P-glycoprotein (Pgp/ABCB1), multidr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.02103.x
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Baclofen (a GABA(B) receptor agonist) is the most commonly used anti-spasticity agent in clinical practice. While effective when administered spinally or systemically, the development of progressive tolerance represents a serious limitation for its long-term use. The goal of the present study was...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00954.x
更新日期:2010-11-01 00:00:00
abstract::We studied the effects of endothelium-derived relaxing factor (EDRF), bovine retractor penis muscle inhibitory factor and sodium nitroprusside, three stimulants of guanylate cyclase, on the in vitro aggregation of washed human platelets. Platelet aggregation induced either by collagen or by the thromboxane A2 analogue...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11221.x
更新日期:1987-04-01 00:00:00
abstract::1 The effect of local elevation of leucocyte cyclic adenosine 3',5'-monophosphate (cyclic AMP) content on the continued migration of leucocytes to a site of acute inflammation was studied in the pleural cavity of rats. 2 Leucocyte cyclic AMP levels were elevated by injecting with the irritant into the pleural cavity d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07742.x
更新日期:1977-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Xaliproden (SR57746A) is a 5-HT(1A) receptor agonist and neurotrophic agent that reduces oxaliplatin-mediated neuropathy in clinical trials. The present study investigated its profile on in vitro transduction, neurochemical responses and acute nociceptive pain tests in rats. EXPERIMENTAL APPROAC...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00249.x
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:It has been extensively reported that the leading anti-diabetic drug, metformin, exerts significant anticancer effects. This hydrophilic, cationic drug requires cation transporters for cellular entry where it activates its intracellular target, the AMPK signalling pathway. However, clinical resul...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14694
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Tumour cell-induced platelet aggregation (TCIPA) facilitates cancer cell invasion, angiogenesis and the formation of metastatic foci. TCIPA can be modulated by pharmacological inhibitors of MMP-2 and ADP; however, the COX inhibitor aspirin did not prevent TCIPA. In this study, we have tested the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01794.x
更新日期:2012-06-01 00:00:00
abstract::1 delta'-trans-Tetrahydrocannabinol (THC) is more active orally in mice than previously thought, as cataleptic responses occur at doses from 0.06 mg/kg upwards, with peak activity at 2 to 4 h after dosing. These doses and peaks correspond well with the effects in man. 2 Comparison with chlorpromazine in mice shows tha...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb08691.x
更新日期:1979-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:While the 5-HT and Rho-kinase (ROCK) pathways have been implicated in the development of pulmonary arterial hypertension (PAH), the nature of any interactions between them remain unclear. This study investigated a role for ROCK in 5-HT-regulated proliferative responses in lung fibroblasts in vivo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.310
更新日期:2008-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Aucubin, the predominant component of Eucommia ulmoides Oliv., has been shown to have profound effects on oxidative stress. As oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of aucubin on cardiac remodelling and heart ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14164
更新日期:2018-05-01 00:00:00
abstract::1. The role of nitric oxide in the coronary circulation under basal conditions and when exposed to various vasodilator stimuli was studied in instrumented, anaesthetized goats, by examining the action of inhibiting endogenous nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME). 2. In 12 goats, left ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14375.x
更新日期:1992-07-01 00:00:00
abstract::The mechanism of action of prostacyclin (PGI2) on isolated segments of guinea-pig terminal ileum was studied by recording the changes in isometric tension. In these preparations PGI2 (1 nM-1 microM) caused a concentration-dependent increase in muscle tension. This effect was rapid and short-lasting. PGI2-induced contr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10031.x
更新日期:1983-10-01 00:00:00
abstract::1. The prostate function is regulated by androgens and alpha-adrenergic activity. Clinically, antiandrogens and/or alpha(1)-adrenergic antagonists are commonly used to treat symptomatic prostatic hypertrophy. To elucidate the effects of androgen deprivation on prostate contractility via alpha(1)-adrenoceptor, the char...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703706
更新日期:2000-12-01 00:00:00