Chronic inflammation in the respiratory tract and ciliary dyskinesia

Grzela, Katarzyna; Zagórska, Wioletta; Jankowska‐Steifer, Ewa; Grzela, Tomasz

doi:10.5114/ceji.2013.34369

Cited by 5 publications

(5 citation statements)

References 60 publications

(87 reference statements)

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“…In a previous study of welders with and without symptoms, gene expression analysis in induced sputum [ 48 ] revealed that genes differentially expressed following welding fume exposure were connected to responses related to tissue damage, immune defense, and inflammation, and one gene that was highly expressed by the asthmatic subjects codes for MMP25, a membrane bound metalloproteinase. Prolonged or frequent exposure to pro-inflammatory agents might promote the development of chronic inflammation with associated damage and transformation of the respiratory epithelium [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix

et al. 2018

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Background Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects.MethodsIn an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC–MS/MS and a targeted selected reaction monitoring LC–MS/MS analyzing 130 proteins and four in vivo peptide degradation products.ResultsThe analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways.ConclusionExposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.Electronic supplementary materialThe online version of this article (10.1186/s12014-018-9196-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix

et al. 2018

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“…These facts have been confirmed in primary and secondary ciliary dyskinesia or cystic fibrosis. The former is related to the ciliary dysfunction as a consequence of defects in the ciliary structure based on the genetic mutations or inflammatory mediators and pH of the cilia environment, respectively (Rossman et al, 1984;Bisgaard and Pedersen, 1987;Clary-Meinesz et al, 1998;Gomperts et al, 2007;Grzela et al, 2013). The latter is caused by impaired epithelium hydration with high mucus viscosity as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.…”

Section: Cilia In Mucociliary Clearancementioning

confidence: 99%

Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors

2020

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Mucociliary clearance is an essential airway defense mechanism dependent predominantly on the proper ciliary function and mucus rheology. The crucial role of cilia is evident in`a variety of respiratory diseases, as the ciliary dysfunction is associated with a progressive decline in lung function over time. The activity of cilia is under supervision of multiple physiological regulators, including second messengers. Their role is to enable a movement in coordinated metachronal waves at certain beat frequency. Ciliary function can be modulated by various stimuli, including agents from the group of beta 2 agonists, cholinergic drugs, and adenosine triphosphate (ATP). They trigger cilia to move faster in response to elevated cytoplasmic Ca 2+ originated from intracellular sources or replenished from extracellular space. Well-known cilia-stimulatory effect of Ca 2+ ions can be abolished or even reversed by modulating the phosphodiesterase (PDE)-mediated breakdown of cyclic adenosine monophosphate (cAMP) since the overall change in ciliary beating has been dependent on the balance between Ca 2+ ions and cAMP. Moreover, in chronic respiratory diseases, high ATP levels may contribute to cAMP hydrolysis and thus to a decrease in the ciliary beat frequency (CBF). The role of PDE inhibitors in airway cilia-driven transport may help in prevention of progressive loss of pulmonary function often observed despite current therapy. Furthermore, administration of selective PDE inhibitors by inhalation lowers the risk of their systemic effects. Based on this review we may conclude that selective (PDE1, PDE4) or dual PDE inhibitors (PDE3/4) increase the intracellular level of cyclic nucleotides in airway epithelial cells and thus may be an important target in the development of new inhaled mucokinetic agents. Further research is required to provide evidence of their effectiveness and feasibility regarding their cilia-modulating properties.

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“…As mentioned previously, the main trigger of inflammatory response in COPD is usually tobacco smoke or other inhaled constituents of air pollution (Jeffery 2001a ). The prolonged or frequent exposure to pro-inflammatory agents may promote the development of chronic form of inflammation with damage and metaplasia of the respiratory epithelium (Grzela et al 2013 ; Haswell et al 2010 ; Lapperre et al 2007 ).…”

Section: Airway Remodelingmentioning

confidence: 99%

“…COPD and asthma, although significantly different in their initial or stable stages, display more immunologic and molecular similarities in their severe forms and exacerbations. High local concentrations of pro-inflammatory cytokines/chemokines and fibrosis-promoting factors maintain the already initiated process (Decramer et al 2012 ; Grzela et al 2013 ; Rahman and Adcock 2006 ). A long list of key players involved in the process includes IL-8, TNF, fibroblast growth factor, insulin-like growth factor and, especially, transforming growth factor (TGF)-β (Holgate et al 1999 ).…”

Section: Airway Remodelingmentioning

confidence: 99%

Airway Remodeling in Chronic Obstructive Pulmonary Disease and Asthma: the Role of Matrix Metalloproteinase-9

Grzela

Litwiniuk

Zagórska

et al. 2015

Arch. Immunol. Ther. Exp.

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Chronic obstructive pulmonary disease (COPD) and asthma are both associated with airflow restriction and progressive remodeling, which affect the respiratory tract. Among various biological factors involved in the pathomechanisms of both diseases, proteolytic enzymes—matrix metalloproteinases (MMPs)—play an important role, especially MMP-9. In this review, the authors discuss the current topics of research concerning the possible role of MMP-9 in both mentioned diseases. They include the analysis of protein levels, nucleotide polymorphisms of MMP-9 gene and their possible correlation with asthma and COPD. Finally, the authors refer to the studies on MMP-9 inhibition as a new perspective for increasing the effectiveness of treatment in asthma and COPD.

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Chronic inflammation in the respiratory tract and ciliary dyskinesia

Abstract: Abstract

Cited by 5 publications

References 60 publications

Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix

Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix

Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors

Airway Remodeling in Chronic Obstructive Pulmonary Disease and Asthma: the Role of Matrix Metalloproteinase-9

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