Abstract:
:Mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a protein with anti-inflammatory properties and the archetypal member of the dual-specificity phosphatases (DUSPs) family that have emerged over the past decade as playing an instrumental role in the regulation of airway inflammation. Not only does MKP-1 serve a critical role as a negative feedback effector, controlling the extent and duration of pro-inflammatory MAPK signalling in airway cells, upregulation of this endogenous phosphatase has also emerged as being one of the key cellular mechanism responsible for the beneficial actions of clinically-used respiratory medicines, including β2-agonists, phosphodiesterase inhibitors and corticosteroids. Herein, we review the role and regulation of MKP-1 in the context of airway inflammation. We initially outline the structure and biochemistry of MKP-1 and summarise the multi-layered molecular mechanisms responsible for MKP-1 production more generally. We then focus in on some of the key in vitro studies in cell types relevant to airway disease that explain how MKP-1 can be regulated in airway inflammation at the transcriptional, post-translation and post-translational level. And finally, we address some of the potential challenges with MKP-1 upregulation that need to be explored further to fully exploit the potential of MKP-1 to repress airway inflammation in chronic respiratory disease.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Moosavi SM,Prabhala P,Ammit AJdoi
10.1186/s12931-017-0637-3subject
Has Abstractpub_date
2017-08-10 00:00:00pages
154issue
1eissn
1465-9921issn
1465-993Xpii
10.1186/s12931-017-0637-3journal_volume
18pub_type
杂志文章,评审abstract::Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century. The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD. Our understanding of the key molecular mechanisms which drive the pathologi...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-019-1017-y
更新日期:2019-03-04 00:00:00
abstract:BACKGROUND:Little is known about the association between cigarette smoking and asthma severity. We assessed smoking as a determinant of disease severity and control in a cohort of clinic-referred allergic subjects who developed new onset asthma. METHODS:Allergic rhinitis subjects with no asthma (n = 371) were followed...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-16
更新日期:2011-01-24 00:00:00
abstract:BACKGROUND:The patterns of mandibular movements (MM) during sleep can be used to identify increased respiratory effort periodic large-amplitude MM (LPM), and cortical arousals associated with "sharp" large-amplitude MM (SPM). We hypothesized that Cheyne Stokes breathing (CSB) may be identified by periodic abnormal MM p...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0551-8
更新日期:2017-04-20 00:00:00
abstract:BACKGROUND:Idiopathic and toxic pulmonary fibrosis are severe diseases starting classically in the subpleural area of the lung. It has recently been suggested that pleural mesothelial cells acquire a myofibroblast phenotype under fibrotic conditions induced by TGF-β1 or bleomycin. The importance and role of inflammatio...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0475-8
更新日期:2016-11-29 00:00:00
abstract:BACKGROUND:Functional deterioration in cystic fibrosis (CF) may be reflected by increasing bronchial obstruction and, as recently shown, by ventilation inhomogeneities. This study investigated which physiological factors (airway obstruction, ventilation inhomogeneities, pulmonary hyperinflation, development of trapped ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-138
更新日期:2006-11-30 00:00:00
abstract:RATIONALE:Smoking-induced chronic obstructive pulmonary disease (COPD) is associated with acquired systemic cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Recently, sweat evaporimetry has been shown to efficiently measure β-adrenergic sweat rate and specifically quantify CFTR function in the se...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-15-25
更新日期:2014-02-25 00:00:00
abstract:BACKGROUND:To compare the efficacy and safety of budesonide/formoterol (Symbicort) with formoterol (Oxis) in the treatment of patients with acute asthma who showed evidence of refractoriness to short-acting beta2-agonist therapy. METHODS:In a 3 hour, randomized, double-blind study, a total of 115 patients with acute a...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/1465-9921-7-13
更新日期:2006-01-24 00:00:00
abstract:BACKGROUND:A disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by activated leukocytes, and fibroblasts in vitro. Whether ADAM15 expression is increased in the lungs of COPD patients is not known. METHODS:ADAM15 gene expression and/or protein levels were measured in whole lung and bronchoalveolar lavag...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01446-5
更新日期:2020-07-16 00:00:00
abstract:BACKGROUND:Radiation pneumonitis (RP) is a frequent complication of concurrent chemoradiotherapy (CCRT) and is associated with severe symptoms that decrease quality of life and might result in pulmonary fibrosis or death. The aim of this study is to identify whether pulmonary function test (PFT) abnormalities may predi...
journal_title:Respiratory research
pub_type: 杂志文章,多中心研究
doi:10.1186/s12931-018-0775-2
更新日期:2018-04-24 00:00:00
abstract:BACKGROUND:The aim of the study is to examine the effect of limited and prolonged hyperoxia on neonatal rat lung. This is done by examining the morphologic changes of apoptosis, the expression of ceramide, an important mediator of apoptosis, the expression of inflammatory mediators represented by IL-1beta and the expre...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-100
更新日期:2006-07-26 00:00:00
abstract:BACKGROUND:Using guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC) nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO) production--due to competition with neuronal NO-synthase (nNOS) for the comm...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-6
更新日期:2006-01-12 00:00:00
abstract::The Global Initiative for Asthma (GINA) guidelines do not specify a bronchodilator range for bronchodilator response (BDR) testing and simply recommend a salbutamol dose of 200 to 400 μg. We determined the oscillometric BDR results of children given low-dose (2 puffs, 200 μg) and standard-dose (4 puffs, 400 μg) salbut...
journal_title:Respiratory research
pub_type: 信件,随机对照试验
doi:10.1186/s12931-017-0632-8
更新日期:2017-08-03 00:00:00
abstract:OBJECTIVES:Swimming is one of the most popular forms of physical activity. Pool water is cleaned with chlorine, which - in combination with compounds contained in water - could form chloramines and trichloromethane in the swimmer's lungs. The aim of the present study was to examine the effect of swimming training in an...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01350-y
更新日期:2020-04-15 00:00:00
abstract:BACKGROUND:Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) is an important predictor of poor prognosis, but the molecular mechanisms of muscle weakness in COPD have not been fully elucidated. The aim of this study was to investigate the role of histone deacetylases(HDAC) in skeletal muscle weak...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0588-8
更新日期:2017-05-19 00:00:00
abstract::Reports regarding gender-related differences in COPD expression have provided conflicting results. In the French Initiatives BPCO real-world cohort, which contained 688 patients (146 women) when data were extracted, women were matched with men (1:3 ratio: n = 107:275) on age (5-year intervals) and FEV1 (5% predicted i...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-15-20
更新日期:2014-02-17 00:00:00
abstract:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is chronic fibrosing pneumonia with an unpredictable natural disease history. Functional respiratory imaging (FRI) has potential to better characterize this disease. The aim of this study was to identify FRI parameters, which predict FVC decline in patients with IPF. METH...
journal_title:Respiratory research
pub_type: 临床试验,杂志文章
doi:10.1186/s12931-018-0918-5
更新日期:2018-11-06 00:00:00
abstract::Asthma is a complex inflammatory disorder controlled by both genetic and environmental influences. Multiple genetic analyses have identified the T helper type 2 (Th2) cytokine gene cluster on chromosome 5q as a susceptibility locus for asthma. Recently, the Th2 cytokine interleukin-13 has been shown to be a critical m...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/rr7
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:Azithromycin (Azm) is a macrolide recognized for its disease-modifying effects and reduction in exacerbation of chronic airway diseases. It is not clear whether the beneficial effects of Azm are due to its anti-microbial activity or other pharmacological actions. We have shown that Azm affects the integrity ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1101-3
更新日期:2019-06-24 00:00:00
abstract:BACKGROUND:Generalized hypoxic pulmonary vasoconstriction (HPV) occurring during exposure to hypoxia is a detrimental process resulting in an increase in lung vascular resistance. Nebulization of sodium nitrite has been shown to inhibit HPV. The aim of this project was to investigate and compare the effects of nebuliza...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-11-81
更新日期:2010-06-21 00:00:00
abstract:BACKGROUND:Pulmonary sarcoidosis is an inflammatory disease, characterized by an accumulation of CD4+ lymphocytes and the formation of non-caseating epithelioid cell granulomas in the lungs. The disease either resolves spontaneously or develops into a chronic disease with fibrosis. The neurotrophins nerve growth factor...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-11-156
更新日期:2010-11-08 00:00:00
abstract:BACKGROUND:Pleural effusion (PE) can be divided into benign pleural effusion (BPE) and malignant pleural effusion (MPE). There is no consensus on the identification of lung cancer-associated MPE using the optimal cut-off levels from five common tumor biomarkers (CEA, CYFRA 21-1, CA125, SCC-Ag, and NSE). Therefore, we a...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01557-z
更新日期:2020-10-29 00:00:00
abstract:BACKGROUND:Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH). Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6). METHODS:To determine whether endogenous IL-6 contributes to mediate hypoxic PH and...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-10-6
更新日期:2009-01-27 00:00:00
abstract:RESEARCH QUESTION:There is no widely accepted grading system for IPF disease severity, although physiologic impairment based on pulmonary function testing is frequently employed. We sought to describe clinical and functional characteristics as well as outcomes of patients with severe physiologic impairment. PATIENTS A...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01600-z
更新日期:2021-01-06 00:00:00
abstract:BACKGROUND:Initial combination therapy with ambrisentan and tadalafil reduced the risk of clinical failure events for treatment-naïve participants with pulmonary arterial hypertension (PAH) as compared to monotherapy. Previous studies in PAH have demonstrated greater treatment benefits in more symptomatic participants....
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12931-019-1180-1
更新日期:2019-09-12 00:00:00
abstract:BACKGROUND:The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD. COPD patients have a variety of comorbidities, but little is known about their impact on quality of life. This study was designed to investigate comorbid factors that may contribute to high CAT...
journal_title:Respiratory research
pub_type: 临床试验,杂志文章
doi:10.1186/1465-9921-15-13
更新日期:2014-02-06 00:00:00
abstract:BACKGROUND:Recent research has suggested that the Th1 and Th2 chemokine/cytokine axis contributes to the development of chronic hypersensitivity pneumonitis (HP). Acute exacerbations (AE) are significant factors in the prognosis of chronic HP. Little is known, however, about these biomarkers in association with AE in c...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-14-57
更新日期:2013-05-25 00:00:00
abstract:BACKGROUND:Glucocorticoid (GC) resistance is a major barrier in COPD treatment. We have shown increased expression of the drug efflux pump, Pgp1 in cytotoxic/pro-inflammatory lymphocytes in COPD. Loss of lymphocyte co-stimulatory molecule CD28 (lymphocyte senescence) was associated with a further increase in their pro-...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-014-0161-7
更新日期:2015-01-09 00:00:00
abstract:BACKGROUND:Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone that is required for molecular maturation of various types of collagens. We recently reported that HSP47 serum levels were markedly higher in patients with acute exacerbations of idiopathic pulmonary fibrosis (IPF) when compared with pati...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-14-133
更新日期:2013-11-20 00:00:00
abstract:BACKGROUND:The relationship between the Epworth sleepiness scale (ESS) and the apnea-hypopnea index (AHI) is uncertain and even poor. The major problem associated with the ESS might be a lack of consideration of weight in prediction in clinical practice. Would awarding different item-scores to the four scales of ESS it...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01417-w
更新日期:2020-06-12 00:00:00
abstract:BACKGROUND:Genetic variation may underlie phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD). Genotype specific sub-phenotypes are likely and may underlie the poor replication of previous genetic studies. This study investigated subjec...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-52
更新日期:2008-07-11 00:00:00