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.

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 Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice

Blood ◽  
2011 ◽  
Vol 118 (26) ◽  
pp. 6930-6938 ◽  
Author(s):  
Jennifer N. Lilla ◽  
Ching-Cheng Chen ◽  
Kaori Mukai ◽  
Maya J. BenBarak ◽  
Christopher B. Franco ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Genetic Manipulation ◽  
Allergic Inflammation ◽  
Myeloid Cell ◽  
Hematopoietic Cell ◽  
Cell Populations ◽  
And Function

Abstract It has been reported that the intracellular antiapoptotic factor myeloid cell leukemia sequence 1 (Mcl-1) is required for mast cell survival in vitro, and that genetic manipulation of Mcl-1 can be used to delete individual hematopoietic cell populations in vivo. In the present study, we report the generation of C57BL/6 mice in which Cre recombinase is expressed under the control of a segment of the carboxypeptidase A3 (Cpa3) promoter. C57BL/6-Cpa3-Cre; Mcl-1fl/fl mice are severely deficient in mast cells (92%-100% reduced in various tissues analyzed) and also have a marked deficiency in basophils (58%-78% reduced in the compartments analyzed), whereas the numbers of other hematopoietic cell populations exhibit little or no changes. Moreover, Cpa3-Cre; Mcl-1fl/fl mice exhibited marked reductions in the tissue swelling and leukocyte infiltration that are associated with both mast cell- and IgE-dependent passive cutaneous anaphylaxis (except at sites engrafted with in vitro–derived mast cells) and a basophil- and IgE-dependent model of chronic allergic inflammation, and do not develop IgE-dependent passive systemic anaphylaxis. Our findings support the conclusion that Mcl-1 is required for normal mast cell and basophil development/survival in vivo in mice, and also suggest that Cpa3-Cre; Mcl-1fl/fl mice may be useful in analyzing the roles of mast cells and basophils in health and disease.

scholarly journals Role of epithelial ion transports in inflammatory bowel disease

2016 ◽  
Vol 310 (7) ◽  
pp. G460-G476 ◽  
Author(s):  
Diogo Magalhães ◽  
José Miguel Cabral ◽  
Patrício Soares-da-Silva ◽  
Fernando Magro
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Ionic Transport ◽  
Current Evidence ◽  
Sodium Absorption ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Potassium Secretion ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex pathogenesis. Diarrhea is a highly prevalent and often debilitating symptom of IBD patients that results, at least in part, from an intestinal hydroelectrolytic imbalance. Evidence suggests that reduced electrolyte absorption is more relevant than increased secretion to this disequilibrium. This systematic review analyses and integrates the current evidence on the roles of epithelial Na+-K+-ATPase (NKA), Na+/H+ exchangers (NHEs), epithelial Na+ channels (ENaC), and K+ channels (KC) in IBD-associated diarrhea. NKA is the key driving force of the transepithelial ionic transport and its activity is decreased in IBD. In addition, the downregulation of apical NHE and ENaC and the upregulation of apical large-conductance KC all contribute to the IBD-associated diarrhea by lowering sodium absorption and/or increasing potassium secretion.

scholarly journals The role of epigenetics and immunological imbalance in the etiopathogenesis of psoriasis and psoriatic arthritis

2019 ◽  
Vol 11 ◽  
pp. 1759720X1988650 ◽  
Author(s):  
Lukas Frischknecht ◽  
Matteo Vecellio ◽  
Carlo Selmi
Keyword(s):  
Psoriatic Arthritis ◽  
Unmet Need ◽  
Current Evidence ◽  
Inflammatory Disorder ◽  
Susceptibility Loci ◽  
Trigger Factors ◽  
Chronic Inflammatory Disorder ◽  
Psoriatic Disease ◽  
Environmental Trigger

Psoriasis (Ps) and psoriatic arthritis (PsA) represent a clinical and immunopathogenic continuum, called psoriatic disease, cumulatively affecting approximately 3% of the general population. Psoriatic disease is a chronic inflammatory disorder affecting the skin and musculoskeletal system. The immuno-pathogenesis is characterized by an activation of the TNF/IL-23/IL-17 cytokine axis, leading to an immunologic imbalance of T-cells resident in all affected tissues, mainly entheses. In the majority of cases, skin Ps predates rheumatological manifestations. Secondary to the higher incidence and the availability of mouse models, there is stronger data available on skin Ps, and data are, in most cases, relevant also to PsA. In a widely accepted model, environmental trigger factors like infections or trauma are capable of initiating an inflammatory cascade, ultimately creating a sustained state of chronic inflammation in genetically susceptible individuals. Besides well-known genetic susceptibility loci, epigenetic DNA modifications, which are associated with Ps development have been characterized recently and will be discussed in this article. The current evidence is promising in the possibility to provide new therapeutic avenues and fill the unmet need of patients, for whom current treatments either do not allow the disease to be controlled or must be continued for life.

scholarly journals Discrete and continuum phenotype-structured models for the evolution of cancer cell populations under chemotherapy

2020 ◽  
Vol 15 ◽  
pp. 14 ◽  
Author(s):  
Rebecca E.A. Stace ◽  
Thomas Stiehl ◽  
Mark A.J. Chaplain ◽  
Anna Marciniak-Czochra ◽  
Tommaso Lorenzi
Keyword(s):  
Cancer Cell ◽  
Cell Population ◽  
Evolutionary Dynamics ◽  
Analytical Description ◽  
Chemotherapeutic Agents ◽  
Cell Populations ◽  
Theoretical Ground ◽  
Individual Based Model ◽  
Nonlocal Parabolic Equation ◽  
Epigenetic Drug

We present a stochastic individual-based model for the phenotypic evolution of cancer cell populations under chemotherapy. In particular, we consider the case of combination cancer therapy whereby a chemotherapeutic agent is administered as the primary treatment and an epigenetic drug is used as an adjuvant treatment. The cell population is structured by the expression level of a gene that controls cell proliferation and chemoresistance. In order to obtain an analytical description of evolutionary dynamics, we formally derive a deterministic continuum counterpart of this discrete model, which is given by a nonlocal parabolic equation for the cell population density function. Integrating computational simulations of the individual-based model with analysis of the corresponding continuum model, we perform a complete exploration of the model parameter space. We show that harsher environmental conditions and higher probabilities of spontaneous epimutation can lead to more effective chemotherapy, and we demonstrate the existence of an inverse relationship between the efficacy of the epigenetic drug and the probability of spontaneous epimutation. Taken together, the outcomes of the model provide theoretical ground for the development of anticancer protocols that use lower concentrations of chemotherapeutic agents in combination with epigenetic drugs capable of promoting the re-expression of epigenetically regulated genes.

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 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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