Airway Remodeling in Asthma: Therapeutic Implications of Mechanisms

Physiology ◽  
2005 ◽  
Vol 20 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Robert J. Homer ◽  
Jack A. Elias
Keyword(s):  
Inflammatory Mediators ◽  
Structural Changes ◽  
Tissue Injury ◽  
Airway Remodeling ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Therapeutic Implications ◽  
Downstream Signaling ◽  
Signaling Events

Asthma is currently recognized as a chronic inflammatory disorder of the airways that leads to tissue injury and subsequent structural changes collectively called airway remodeling. Transgenic modeling of inflammatory mediators allows for the discovery of unexpected effects, dissection of downstream signaling events, and clues to future therapies.

scholarly journals Neutrophil-Initiated Myocardial Inflammation and Its Modulation by B-Type Natriuretic Peptide: A Potential Therapeutic Target

2018 ◽  
Vol 20 (1) ◽  
pp. 129 ◽  
Author(s):  
Saifei Liu ◽  
Yuliy Chirkov ◽  
John Horowitz
Keyword(s):  
Heart Failure ◽  
Nadph Oxidase ◽  
Natriuretic Peptide ◽  
Tissue Injury ◽  
Diastolic Heart Failure ◽  
Cardiac Injury ◽  
Myocardial Inflammation ◽  
Inflammatory Disorder ◽  
Therapeutic Implications ◽  
Vasomotor Dysfunction

Activation of neutrophils is a critically important component of the innate immune response to bacterial and chemical stimuli, and culminates in the “neutrophil burst”, which facilitates neutrophil phagocytosis via the release of superoxide anion radical (O2−) from NADPH oxidase. Excessive and/or prolonged neutrophil activation results in substantial tissue injury and increases in vascular permeability—resulting in sustained tissue infiltration with neutrophils and monocytes, and persistent vasomotor dysfunction. Cardiovascular examples of such changes include acute and chronic systolic and diastolic heart failure (“heart failure with preserved ejection fraction”), and the catecholamine-induced inflammatory disorder takotsubo syndrome. We have recently demonstrated that B-type natriuretic peptide (BNP), acting via inhibition of activation of neutrophil NADPH oxidase, is an important negative modulator of the “neutrophil burst”, though its effectiveness in limiting tissue injury is partially lost in acute heart failure. The potential therapeutic implications of these findings, regarding the development of new means of treating both acute and chronic cardiac injury states, are discussed.

Total Eosinophils, Ecp And IL-5 In Peripheral Blood During Treatment with Inhaled Corticosteroids in Patients with Asthma

2015 ◽  
Vol 69 (2) ◽  
pp. 55-58
Author(s):  
Deska Dimitrievska ◽  
Marija Zdraveska ◽  
Dejan Todevski
Keyword(s):  
Inflammatory Reaction ◽  
Peripheral Blood ◽  
Inhaled Corticosteroids ◽  
Airway Remodeling ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Reversible Airway Obstruction ◽  
The Mean ◽  
The University ◽  
Main Attribute

AbstractIntroduction. The main attribute of asthma is inflammation, which leads to airway remodeling, bronchial hyperreactivity and reversible or partly reversible airway obstruction. According to GINA, asthma is a chronic inflammatory disorder of the airways in which many cells play a role, in particular mast cells, eosinophils (Eo), and T lymphocytes. Many cells and mediators take part in creating the asthmatic inflammatory reaction, but eosinophils play a central role. The aim of this study was to show the values of biological inflammatory markers (IL-5 and Eo).Methods. Patients with severe asthma, 22 (73.33%) female and 8 (26.66%) male, aged 18-65 years were included in the study. The mean age was 35.30 ±9.65 years. Patients were treated with spray Beclomethasone dipropionate of 250 μg at doses from 1000 to 2000 μg/per day.Results. This study included 30 patients of the University Clinic of Pulmology and Allergology, Skopje, with confirmed bronchial asthma, treated with ICS. In all of the patients we monitored Eo count, ECP and IL-5 in peripheral blood at the beginning of the study, after 2 and 6 months treatment. During treatment with ICS we registered changes in all of the tested parameters.Conclusion. ICS objectively suppress the inflammatory reaction in asthma and the biological markers (IL-5, Eo and ECP), which we have monitored, can measure the accomplished effect. They could be used in everyday practice, not only as diagnostic parameters but also as valid therapeutic guides in treatment of asthma.

scholarly journals Mast Cells, Cytokines and Asthma

1994 ◽  
Vol 1 (2) ◽  
pp. 118-127 ◽  
Author(s):  
Anthony E Redington ◽  
Peter H Howarth
Keyword(s):  
Mast Cells ◽  
Cell Population ◽  
Structural Changes ◽  
Late Phase ◽  
Allergic Inflammation ◽  
Current Evidence ◽  
Cell Populations ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Cellular Events

The appreciation that asthma is a chronic inflammatory disorder of the airways has led to a reappraisal of the importance of different cell populations within the bronchial mucosa with respect to their role in the regulation of the cellular events in this disease. While mast cell degranulation has been implicated in the acute allergic bronchoconstrictor response, activation of this cell population has not been considered relevant to either the late phase inflammatory cell influx within the airways following allergen bronchoprovocation or to the mucosa! eosinophilia in chronic clinical disease. As such, attention has focused on the T lymphocyte as an orchestrator of these cellular events on account of its ability to synthesize and release cytokines relevant to the allergic process. It is now, however, realized that many cell populations within the airways are able to generate cytokines comparable with and complimentary to those produced by T lymphocytes and that asthma cannot be considered an inflammatory airway disorder dependent upon activation of one single cell population. This review details the current evidence that airway mast cells synthesize, store and release cytokines relevant to allergic inflammation and considers their potential involvement not only in the cellular influx within the airways but also in the fibrotic structural changes which are evident in chronic disease.

Fine Structural Changes in the Adenohypophyses of Rats Following Destruction of the Pituitary Stalk

1977 ◽  
Vol 35 ◽  
pp. 496-497
Author(s):  
K. Kovacs ◽  
E. Horvath ◽  
J. M. Bilbao ◽  
F. A. Laszlo ◽  
I. Domokos
Keyword(s):  
Structural Changes ◽  
Tissue Injury ◽  
Anterior Lobe ◽  
Uranyl Acetate ◽  
Male Rats ◽  
Pituitary Stalk ◽  
Sequence Of Events ◽  
Pituitary Glands ◽  
Electrolytic Lesions ◽  
Ultrathin Sections

Electrolytic lesions of the pituitary stalk in rats interrupt adenohypophysial blood flow and result in massive infarction of the anterior lobe. In order to obtain a deeper insight into the morphogenesis of tissue injury and to reveal the sequence of events, a fine structural investigation was undertaken on adenohypophyses of rats at various intervals following destruction of the pituitary stalk.The pituitary stalk was destroyed electrolytically, with a Horsley-Clarke apparatus on 27 male rats of the R-Amsterdam strain, weighing 180-200 g. Thirty minutes, 1,2,4,6 and 24 hours after surgery the animals were perfused with a glutaraldehyde-formalin solution. The skulls were then opened and the pituitary glands removed. The anterior lobes were fixed in glutaraldehyde-formalin solution, postfixed in osmium tetroxide and embedded in Durcupan. Ultrathin sections were stained with uranyl acetate and lead citrate and investigated with a Philips 300 electron microscope.

scholarly journals Redox Imbalance in T Cell-Mediated Skin Diseases

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Saveria Pastore ◽  
Liudmila Korkina
Keyword(s):  
Oxidative Stress ◽  
Atopic Dermatitis ◽  
Contact Dermatitis ◽  
Skin Diseases ◽  
Redox Balance ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Physical Chemical ◽  
Chemical Oxidants ◽  
Beneficial Outcome

The skin is permanently exposed to physical, chemical, and biological aggression by the environment. In addition, acute and chronic inflammatory events taking place in the skin are accompanied by abnormal release of pro-oxidative mediators. In this paper, we will briefly overview the homeostatic systems active in the skin to maintain the redox balance and also to counteract abnormal oxidative stress. We will concentrate on the evidence that a local and/or systemic redox dysregulation accompanies the chronic inflammatory disorder events associated to psoriasis, contact dermatitis, and atopic dermatitis. We will also discuss the fact that several well-established treatments for the therapy of chronic inflammatory skin disorders are based on the application of strong physical or chemical oxidants onto the skin, indicating that, in selected conditions, a further increase of the oxidative imbalance may lead to a beneficial outcome.

scholarly journals Syndecan Transmembrane Domain Specifically Regulates Downstream Signaling Events of the Transmembrane Receptor Cytoplasmic Domain

2021 ◽  
Vol 22 (15) ◽  
pp. 7918
Author(s):  
Jisun Hwang ◽  
Bohee Jang ◽  
Ayoung Kim ◽  
Yejin Lee ◽  
Joonha Lee ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Growth Factor Receptor ◽  
Cytoplasmic Domain ◽  
Nih3t3 Cells ◽  
C Elegans ◽  
Downstream Signaling ◽  
Downstream Effectors ◽  
Signaling Events

Despite the known importance of the transmembrane domain (TMD) of syndecan receptors in cell adhesion and signaling, the molecular basis for syndecan TMD function remains unknown. Using in vivo invertebrate models, we found that mammalian syndecan-2 rescued both the guidance defects in C. elegans hermaphrodite-specific neurons and the impaired development of the midline axons of Drosophila caused by the loss of endogenous syndecan. These compensatory effects, however, were reduced significantly when syndecan-2 dimerization-defective TMD mutants were introduced. To further investigate the role of the TMD, we generated a chimera, 2eTPC, comprising the TMD of syndecan-2 linked to the cytoplasmic domain of platelet-derived growth factor receptor (PDGFR). This chimera exhibited SDS-resistant dimer formation that was lost in the corresponding dimerization-defective syndecan-2 TMD mutant, 2eT(GL)PC. Moreover, 2eTPC specifically enhanced Tyr 579 and Tyr 857 phosphorylation in the PDGFR cytoplasmic domain, while the TMD mutant failed to support such phosphorylation. Finally, 2eTPC, but not 2eT(GL)PC, induced phosphorylation of Src and PI3 kinase (known downstream effectors of Tyr 579 phosphorylation) and promoted Src-mediated migration of NIH3T3 cells. Taken together, these data suggest that the TMD of a syndecan-2 specifically regulates receptor cytoplasmic domain function and subsequent downstream signaling events controlling cell behavior.

THE ROLE OF INFLAMMATORY MEDIATORS IN EPILEPSY: FOCUS ON DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHIES AND THERAPEUTIC IMPLICATIONS

2021 ◽  
pp. 106588
Author(s):  
Alessandro Orsini ◽  
Thomas Foiadelli ◽  
Giorgio Costagliola ◽  
Alexandre Michev ◽  
Rita Consolini ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Epileptic Encephalopathies ◽  
Therapeutic Implications

scholarly journals Rituximab Treatment in a Patient with Kimura Disease and Membranous Nephropathy: Case Report

2021 ◽  
pp. 116-123
Author(s):  
Roald Vissing-Uhre ◽  
Alastair Hansen ◽  
Susanne Frevert ◽  
Ditte Hansen
Keyword(s):  
Case Report ◽  
Membranous Nephropathy ◽  
Neck Region ◽  
Renal Diseases ◽  
Kimura’S Disease ◽  
Inflammatory Disorder ◽  
Kimura Disease ◽  
Chronic Inflammatory Disorder ◽  
Eosinophil Granulocytes ◽  
Anti Cd20

Kimura disease (KD) is a chronic, inflammatory disorder with slowly developing subcutaneous tumor-like swellings, often occurring in the head and neck region. KD is diagnosed based on histology, elevated levels of immunoglobulin type E, and increased peripheral eosinophil granulocytes. KD may coexist with glomerular renal diseases, and this case report is based on a patient with KD-associated membranous nephropathy. Patients with membranous nephropathy without KD have demonstrated responsiveness to treatment with monoclonal anti-CD20 antibodies. This case report is the first to investigate the effect of rituximab treatment in a patient with KD-associated membranous nephropathy. A 30-year-old Italian man living in Denmark was diagnosed with Kimura’s disease based on subcutaneous nodules with eosinophil angiolymphoid hyperplasia. The patient was admitted to the hospital due to nephrotic syndrome. Serology showed eosinophil granulocytosis and negative PLA2-receptor antibody. Renal biopsy showed membranous nephropathy, and the patient was treated with systemic methylprednisolone followed by cyclosporin and then cyclophosphamide with only partial remission. Ultimately, treatment with intravenous rituximab was initiated, which resulted in overall remission and no nephrotic relapses at 30 months of follow-up. Thus, intravenous rituximab effectively decreased proteinuria and prevented nephrotic relapses in a patient with treatment-refractory membranous nephropathy due to KD.

scholarly journals Serum-derived extracellular vesicles inhibit osteoclastogenesis in active-phase patients with SAPHO syndrome

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110069
Author(s):  
Yanpan Gao ◽  
Yanyu Chen ◽  
Lun Wang ◽  
Chen Li ◽  
Wei Ge
Keyword(s):  
Bone Metabolism ◽  
Extracellular Vesicles ◽  
Inflammatory Marker ◽  
Active Phase ◽  
Sapho Syndrome ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Reactive Protein ◽  
Amyloid A

Objective: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disorder and the underlying pathogenesis is unclear. In this study, 88 SAPHO patients and 118 healthy controls were recruited to investigate the role of serum-derived extracellular vesicles (SEVs) in SAPHO syndrome. Methods: Quantitative proteomics was applied for SEVs proteome identification, and ELISA and Western blotting was performed to verify the results of mass spectrum data. In vitro osteoclastogenesis and osteogenesis assay was used to confirm the effects of SEVs on bone metabolism. Results: Tandem mass tagging-based quantitative proteomic analysis of SAPHO SEVs revealed differential expressed proteins involved in bone metabolism. Of these, serum amyloid A-1 (SAA1) and C-reactive protein (CRP) were upregulated. Higher SAA1 levels in SAPHO patients were confirmed by ELISA. In addition, SAA1 levels were positively correlated with CRP, an inflammatory marker related to the condition of patients. In vitro celluler studies confirmed that SAPHO SEVs inhibited osteoclastogenesis in patients mainly in the active phase of the disease. Further analysis demonstrated that Nucleolin was upregulated in osteoclasts of active-phase patients under SAPHO SEVs stimulation. Conclusion: In this study, we identified SAA1 as an additional inflammation marker that can potentially assist the diagnosis of SAPHO syndrome, and speculated that Nucleolin is a key regulator of osteoclastogenesis in active-phase patients.

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