Abstract：
BACKGROUND AND PURPOSE:Fibroblast-to-myofibroblast differentiation is associated with scarring, an important issue in corneal surgery. Moxifloxacin (MOX), commonly applied to prevent post-operative infection, would benefit more if it modifies fibroblast-to-myofibroblast differentiation other than antimicrobial activity. Our purpose was to explore whether MOX has anti-fibrotic effect in human corneal fibroblasts (HCFs). EXPERIMENTAL APPROACH:HCFs were incubated in MOX-containing medium concurrently with TGF-β1 (co-treatment), before (pretreatment) or after (post-treatment) adding TGF-β1. HCF contractility was evaluated with a type I collagen gel contraction assay. Expression of α-smooth muscle actin (α-SMA), Smad2, phospho-Smad2-Ser467, Smad4 and Smad7 was determined by immunoblotting. Formation of α-SMA-positive filaments and distribution of active Smad2 were observed under confocal microscopy. Expression of TGF-β receptor types I (TGFBR1) and II (TGFBR2) was assessed with flow cytometry. KEY RESULTS:MOX did not affect gel contractility or α-SMA filament formation in HCFs without TGF-β1 stimulation. MOX did, however, retard HCF-containing gel contractility and α-SMA filament formation following TGF-β1 stimulation in the pretreatment and co-treatment groups but not in the post-treatment group. MOX blocked the expression of Smad2, phospho-Smad2-Ser467 and TGFBR1 under TGF-β1 incubation. Additionally, MOX enhanced Smad7 expression in TGF-β1-incubated HCFs, but did not interfere with TGF-β-triggered Smad2 nuclear translocation or Smad4 expression. CONCLUSIONS AND IMPLICATIONS:MOX inhibited TGF-β-induced fibroblast-to-myofibroblast differentiation via blocking TGFBR1 and enhancing Smad7 expression. MOX should be used before or during surgery to achieve these effects. These results suggest a de novo mechanism by which MOX participates in corneal wound healing.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Chen TC,Chang SW,Wang TYdoi
10.1111/bph.12015subject
Has Abstractpub_date
2013-03-01 00:00:00pages
1341-54issue
6eissn
0007-1188issn
1476-5381journal_volume
168pub_type
杂志文章abstract：:1. In guinea-pigs previously sensitized with ovalbumin, the intra-plantar administration of the antigen induced dose-dependent and sustained oedema. An intense infiltrate of neutrophils and eosinophils was observed at the peak of the oedema (4 h). 2. Oedema induced by ovalbumin at the doses of 50 or 200 micrograms/paw...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13038.x
更新日期：1994-05-01 00:00:00
abstract：:Transient expression in COS-7 cells of the recombinant human 5-hydroxytryptamine (5-HT) h5-HT4(c) receptor isoform led to constitutive activity of the receptor. The 5-HT4 receptor antagonist 2-(cis-3,5-dimethylpiperidino)ethyl 4-amino-5-chloro-2-methoxybenzoate (ML10375) at 1 microM completely abolished the 5-HT (1 mi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702163
更新日期：1998-10-01 00:00:00
abstract：:1. (+)-Tubocurarine, hexamethonium, atropine, ouabain, and removal of potassium from the bathing medium were examined for their effects on indirectly evoked twitches (IT) of mouse phrenic nerve-diaphragm muscles in the presence or absence of neostigmine. 2. Neostigmine increased the amplitude of IT. The twitch potenti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11798.x
更新日期：1989-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Following transient focal stroke, rapid accumulation and activation of neutrophils in the ischaemic region is deleterious due to release of reactive oxygen species and myeloperoxidase (MPO). The purpose of this study was to examine whether AM-36, both a Na+ channel blocker and an antioxidant, aff...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706918
更新日期：2006-11-01 00:00:00
abstract：:YM471, (Z)-4'-[4,4-difluoro-5-[2-(4-dimethylaminopiperidino)-2-oxoethylidene]-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl]-2-phenylbenzanilide monohydrochloride, is a newly synthesized potent vasopressin (AVP) receptor antagonist. Its effects on binding to and signal transduction by cloned human AVP receptors (V(1...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704117
更新日期：2001-07-01 00:00:00
abstract：:The chemical trimethylcyclohexanol (TMC) is closely related to menthol, the major component of a terpene preparation with known choleretic and cholelitholytic activity. Its effects on hepatic cholesterol synthesis and bile secretion were examined in the rat. In both acute and long-term dosing experiments TMC significa...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb10759.x
更新日期：1984-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Microglial phenotype and phagocytic activity are deregulated in Parkinson's disease (PD). PPARγ agonists are neuroprotective in experimental PD, but their role in regulating microglial phenotype and phagocytosis has been poorly investigated. We addressed it by using the PPARγ agonist MDG548. EXP...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14214
更新日期：2018-08-01 00:00:00
abstract：:1. Histamine release by compound 48/80 was substantially reduced in a time-dependent manner (maximum at 30 min) by pre-incubating mast cells in calcium-free medium at 37 degrees C but not at 2 degrees C. This effect was optimal at pH 7.0 to 7.5. 2. The re-introduction of calcium (0.1 to 3 mmol/l) restored histamine re...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb07871.x
更新日期：1979-04-01 00:00:00
abstract：:1. The actions of etorphine, morphine and diprenorphine were investigated on neurones of the cerebral cortex and spinal cord of rats anaesthetized with pentobarbitone.2. In the cerebral cortex, intravenous etorphine increased the latency of the primary evoked response to a peripheral nerve stimulus and suppressed the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb06865.x
更新日期：1972-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The synthetic compound efsevin was recently identified to suppress arrhythmogenesis in models of cardiac arrhythmia, making it a promising candidate for antiarrhythmic therapy. Its activity was shown to be dependent on the voltage-dependent anion channel 2 (VDAC2) in the outer mitochondrial membr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.15022
更新日期：2020-07-01 00:00:00
abstract：:1. The effects of the putative gap junction uncoupler, 1-heptanol, on the neurogenic and myogenic contractile responses of guinea-pig vas deferens were studied in vitro. 2. Superfusion of 2.0 mM heptanol for 20-30 min produced the following reversible changes in the biphasic neurogenic contractile response (8 trials):...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702307
更新日期：1999-01-01 00:00:00
abstract：:1. The role of endogenous ADP in platelet aggregation in vivo remains unclear due to the lack of suitable P2T-antagonist probes. This paper describes the potency, selectivity and specificity of the novel P 2T-purinoceptor antagonist, FPL 67085 (2-propylthio-D-beta,gamma-dichloromethylene ATP) both in vitro and in the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15925.x
更新日期：1995-07-01 00:00:00
abstract：:Measurements of affinity and efficacy are fundamental for work on agonists both in drug discovery and in basic studies on receptors. In this review I wish to consider methods for measuring affinity and efficacy at G protein coupled receptors (GPCRs). Agonist affinity may be estimated in terms of the dissociation const...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0707672
更新日期：2008-04-01 00:00:00
abstract：:1. The potassium-sparing diuretic, amiloride, has been shown to inhibit the Na/Ca exchange system in various preparations. The effects of this drug have been investigated on the contractions of guinea-pig aortic strips elicited by reduction of external K, by addition of ouabain and by removal of external Na. 2. Amilor...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb10316.x
更新日期：1988-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Pancreatic cancer is characterized by alterations in several key signalling proteins, including increased expression and activity of the Src tyrosine kinase and focal adhesion kinase (FAK), which have been linked to its chemoresistance. Sustained Src inhibition reactivates survival pathways regul...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12855
更新日期：2015-01-01 00:00:00
abstract：:1. The cyclic nucleotide phosphodiesterase (PDE) of guinea-pig eosinophils was partially characterized and the effects of selective inhibitors of PDE isoenzymes upon opsonized zymosan (OZ)-stimulated respiratory burst were studied. 2. PDE activity in eosinophil lysates appeared to be membrane-associated, displayed sub...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb09790.x
更新日期：1991-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The present study investigated whether the pathophysiological changes induced by burn and smoke inhalation are modulated by parenteral administration of Na(2)S, a H(2)S donor. EXPERIMENTAL APPROACH:The study used a total of 16 chronically instrumented, adult female sheep. Na(2)S was administered...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00411.x
更新日期：2009-11-01 00:00:00
abstract：:1. The effects of capsaicin on voltage-gated Ca2+ currents (ICa), and intracellular Ca2+ concentrations [( Ca2+]i) in cultured dorsal root ganglion (DRG) neurones of the rat were examined in vitro by use of combined patch clamp-microfluorometric recordings. 2. Under voltage-clamp conditions, capsaicin (0.1-10 microM) ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12725.x
更新日期：1990-10-01 00:00:00
abstract：:1 The N6-2-O-dibutyryl derivative of adenosine 3',5'-monophosphate (db cyclic AMP) has been micro-injected into the third cerebral ventricle of the unanaesthetized, restrained mouse and the effects on body temperature and thermoregulatory activities observed. 2 Db cyclic AMP (4, 16 and 32 micrograms) injected intracer...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb08723.x
更新日期：1980-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:As a hallmark of glioblastoma multiforme (GBM), CD44 plays a crucial role in promoting glioblastoma stem cell (GSC) stemness phenotypes and multiple drug resistance. The therapeutic potential of CD44 has been validated by the clinical successes of several CD44 inhibitors, including antibodies and...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.15030
更新日期：2020-07-01 00:00:00
abstract：:1. A murine macrophage cell line, J774, expressed nitric oxide (NO) synthase activity in response to interferon-gamma (IFN-gamma, 10 u ml-1) plus lipopolysaccharide (LPS, 10 ng ml-1). The enzyme activity was first detectable 6 h after incubation, peaked at 12 h and became undetectable after 48 h. 2. The decline in the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb12886.x
更新日期：1993-03-01 00:00:00
abstract：:(1) Rapid desensitization of ligand-gated ion channel receptors can alter the apparent activity of receptor modulators, as well as make detection of fast-channel activation difficult. Investigation of the antagonist pharmacology of ATP-sensitive homomeric P2X3 receptors is limited by agonist-evoked fast-desensitizatio...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705411
更新日期：2003-09-01 00:00:00
abstract：:1 Adenosine 5'-triphosphate (ATP) is an enteric neurotransmitter which acts at purine receptors on intestinal nerve and muscle. This study set out to shed light on the receptor mechanisms by which exogenous and endogenous ATP influences intestinal peristalsis. 2 Peristalsis in isolated segments of the guinea-pig small...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702808
更新日期：1999-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Sulphatides are sulphated glycosphingolipids expressed on the surface of many cell types, particularly neurones. Changes in sulphatide species or content have been associated with epilepsy and Alzheimer's disease. As the large conductance, calcium sensitive K(+) channel (BK(Ca)) are modulated by ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706947
更新日期：2006-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The aggregation of α-synuclein is connected to the pathology of Parkinson's disease and prolyl oligopeptidase (PREP) accelerates the aggregation of α-synuclein in vitro. The aim of this study was to investigate the effects of a PREP inhibitor, KYP-2047, on α-synuclein aggregation in cell lines ov...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.01846.x
更新日期：2012-06-01 00:00:00
abstract：:The effects of a new selective beta1-adrenoceptor agonist, (--)-1-(4-hydroxyphenoxy)-3-isopropyl-amino-propanol-2-hydrochloride (H 133/22), on amylase secretion from the rat parotid gland were investigated in an in vitro system. The results were compared to the secretory responses obtained with noradrenaline, adrenali...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb08470.x
更新日期：1978-03-01 00:00:00
abstract：:1. The roles of nitric oxide (NO), superoxide anion (O(2)(-)), and hydrogen peroxide (H(2)O(2)) in the modulation of spontaneous tone were investigated in isolated aorta from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. 2. Increases in preload from 1 to 5 g were accompanied by increases in spontaneous to...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705557
更新日期：2004-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Inhibitors of phosphodiesterase 5 (PDE5) affect signalling pathways by elevating cGMP, which is a second messenger involved in processes of neuroplasticity. In the present study, the effects of the PDE5 inhibitor, sildenafil, on the pathological features of Alzheimer's disease and on memory-relat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01517.x
更新日期：2011-12-01 00:00:00
abstract：:1. Two preparations, a segment of the ileum and the myenteric plexuslongitudinal muscle preparation, have been used for an analysis of the inhibitory effects of adrenaline, noradrenaline and isoprenaline on the contractor responses of the longitudinal muscle to acetylcholine or to electrical, coaxial or field, stimula...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb12903.x
更新日期：1970-06-01 00:00:00
abstract：:1. The release of 5-hydroxytryptamine (5-HT) from the cerebral cortex and caudate nucleus of brainstem-transected cats and from the cerebral cortex of rats anaesthetized with urethane was determined by radioenzymatic and biological assay. 2. The stimulation of nucleus linearis intermedius of raphe doubles the basal 5-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb07863.x
更新日期：1979-04-01 00:00:00
