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Asthma pathogenesis

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https://www.readbyqxmd.com/read/28424691/increased-autophagy-related-5-gene-expression-is-associated-with-collagen-expression-in-the-airways-of-refractory-asthmatics
#1
Audrey H Poon, David F Choy, Fazila Chouiali, Rakhee K Ramakrishnan, Bassam Mahboub, Severine Audusseau, Andrea Mogas, Jeffrey M Harris, Joseph R Arron, Catherine Laprise, Qutayba Hamid
BACKGROUND: Fibrosis, particularly excessive collagen deposition, presents a challenge for treating asthmatic individuals. At present, no drugs can remove or reduce excessive collagen in asthmatic airways. Hence, the identification of pathways involved in collagen deposition would help to generate therapeutic targets to interfere with the airway remodeling process. Autophagy, a cellular degradation process, has been shown to be dysregulated in various fibrotic diseases, and genetic association studies in independent human populations have identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28423590/neutralization-of-interleukin-17-suppresses-allergic-rhinitis-symptoms-by-downregulating-th2-and-th17-responses-and-upregulating-the-treg-response
#2
Zhao Wei Gu, Yun Xiu Wang, Zhi Wei Cao
Allergic rhinitis (AR) has long been considered to predominantly involve the actions of Th2 cells, with relatively small contributions from Th1 cells. In recent years, the discovery of Th17 and regulatory T (Treg) cells has rendered the Th1/Th2 balance paradigm more complex and expanded our understanding of the pathogenesis of AR. IL-17, a key cytokine produced by Th17 cells, is known to induce allergen-specific Th2 cell activation, eosinophil and neutrophil accumulation, and serum IgE production in asthma; all of these features may play important roles in AR...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416592/-wnt-er-is-coming-wnt-signalling-in-chronic-lung-diseases
#3
H A Baarsma, M Königshoff
Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD...
April 17, 2017: Thorax
https://www.readbyqxmd.com/read/28416135/all-the-rage-in-lung-disease-the-receptor-for-advanced-glycation-endproducts-rage-is-a-major-mediator-of-pulmonary-inflammatory-responses
#4
REVIEW
Elizabeth A Oczypok, Timothy N Perkins, Tim D Oury
The receptor for advanced glycation endproducts (RAGE) is a pro-inflammatory pattern recognition receptor (PRR) that has been implicated in the pathogenesis of numerous inflammatory diseases. It was discovered in 1992 on endothelial cells and was named for its ability to bind advanced glycation endproducts and promote vascular inflammation in the vessels of patients with diabetes. Further studies revealed that RAGE is most highly expressed in lung tissue and spurred numerous explorations into RAGE's role in the lung...
March 18, 2017: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/28408397/the-il-31-il-31-receptor-axis-general-features-and-role-in-tumor-microenvironment
#5
REVIEW
Elisa Ferretti, Anna Corcione, Vito Pistoia
IL-31 is a recently identified cytokine with a well-defined role in the pathogenesis of pruritus. IL-31, whose production is induced by IL-4 and IL-33, binds a heterodimeric receptor (R) composed of the exclusive IL-31RA chain and the shared oncostatin M R. Signaling through the IL-31R involves the MAPK, PI3K/AKT and Jak/STAT pathways. Different variants and isoforms of IL-31RA with different signaling activities have been identified. IL-31 is produced predominantly by circulating Th2 lymphocytes and skin-homing CLA(+)CD45RO(+) T cells...
April 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28407346/vitamin-d-receptor-gene-polymorphisms-in-serbian-patients-with-bronchial-asthma-a-case-control-study
#6
Milena Despotovic, Tatjana Jevtovic Stoimenov, Ivana Stankovic, Jelena Basic, Dusica Pavlovic
Vitamin D and single nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR) gene are potentially involved in the pathogenesis of bronchial asthma (BA); however, precise mechanisms by which vitamin D reduces the inflammation and the role of VDR SNPs in BA are not completely understood. The aim of this study was to examine the possible associations of FokI, BsmI, ApaI and TaqI SNPs with BA. A total of 168 subjects were screened for VDR SNPs using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method...
April 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28401621/mouse-models-of-severe-asthma-understanding-the-mechanisms-of-steroid-resistance-tissue-remodelling-and-disease-exacerbation
#7
REVIEW
Steven Maltby, Hock L Tay, Ming Yang, Paul S Foster
Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for individuals with severe asthma are often ineffective. Mouse models are useful to identify mechanisms underlying disease pathogenesis and for the preclinical assessment of new therapies. In fact, existing mouse models have contributed significantly to our understanding of allergic/eosinophilic phenotypes of asthma and facilitated the development of novel targeted therapies (e...
April 11, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28399855/characterisation-of-a-murine-model-of-the-late-asthmatic-response
#8
Katie Baker, Kristof Raemdonck, Robert J Snelgrove, Maria G Belvisi, Mark A Birrell
BACKGROUND: The incidence of asthma is increasing at an alarming rate. While the current available therapies are effective, there are associated side effects and they fail to adequately control symptoms in all patient subsets. In the search to understand disease pathogenesis and find effective therapies hypotheses are often tested in animal models before progressing into clinical studies. However, current dogma is that animal model data is often not predictive of clinical outcome. One possible reason for this is the end points measured such as antigen-challenge induced late asthmatic response (LAR) is often used in early clinical development, but seldom in animal model systems...
April 11, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28397284/altered-fatty-acid-metabolism-and-reduced-stearoyl-coenzyme-a-desaturase-activity-in-asthma
#9
N Rodriguez-Perez, E Schiavi, R Frei, R Ferstl, P Wawrzyniak, S Smolinska, M Sokolowska, N A Sievi, M Kohler, P Schmid-Grendelmeier, D Michalovich, K D Simpson, E M Hessel, M Jutel, M Martin-Fontecha, O Palomares, C A Akdis, L O'Mahony
BACKGROUND: Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely under-explored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and non-obese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. METHODS: Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS...
April 11, 2017: Allergy
https://www.readbyqxmd.com/read/28392332/type-2-innate-lymphoid-cells-disrupt-bronchial-epithelial-barrier-integrity-by-targeting-tight-junctions-via-il-13-in-asthma
#10
Kazunari Sugita, Catherine A Steer, Itziar Martinez-Gonzalez, Can Altunbulakli, Hideaki Morita, Francesc Castro-Giner, Terufumi Kubo, Paulina Wawrzyniak, Beate Rückert, Katsuko Sudo, Susumu Nakae, Kenji Matsumoto, Liam O'Mahony, Mübeccel Akdis, Fumio Takei, Cezmi A Akdis
BACKGROUND: Bronchial epithelial barrier leakiness and type 2 innate lymphoid cells (ILC2s) have been separately linked to asthma pathogenesis, however the influence of ILC2s on bronchial epithelial barrier has not been previously investigated. OBJECTIVE: We investigated the role of ILC2s in the regulation of bronchial epithelial tight junctions (TJs) and barrier function both in bronchial epithelial cells of asthmatic and healthy individuals and general ILC- and ILC2-deficient mice...
April 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28391979/maintenance-of-pathogenic-th2-cells-in-allergic-disorders
#11
REVIEW
Kenta Shinoda, Kiyoshi Hirahara, Toshinori Nakayama
Immunological memory is an important protective mechanism that enables host organisms to respond rapidly and vigorously to pathogens that have been previously encountered. In addition to the protective function, memory CD4(+) T helper (Th) cells play a central role in the pathogenesis of chronic inflammatory disorders, including asthma. Recently, several investigators have identified phenotypically and functionally distinct memory Th2 cell subsets that produce IL-5. These memory Th2 cell subsets play an important role in the pathology of allergic inflammation and function as memory-type "pathogenic Th2 (Tpath2) cells" both in mice and humans...
April 5, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28388380/acquired-amino-acid-deficiencies-a-focus-on-arginine-and-glutamine
#12
Claudia R Morris, Jill Hamilton-Reeves, Robert G Martindale, Menaka Sarav, Juan B Ochoa Gautier
Nonessential amino acids are synthesized de novo and therefore not diet dependent. In contrast, essential amino acids must be obtained through nutrition since they cannot be synthesized internally. Several nonessential amino acids may become essential under conditions of stress and catabolic states when the capacity of endogenous amino acid synthesis is exceeded. Arginine and glutamine are 2 such conditionally essential amino acids and are the focus of this review. Low arginine bioavailability plays a pivotal role in the pathogenesis of a growing number of varied diseases, including sickle cell disease, thalassemia, malaria, acute asthma, cystic fibrosis, pulmonary hypertension, cardiovascular disease, certain cancers, and trauma, among others...
April 2017: Nutrition in Clinical Practice
https://www.readbyqxmd.com/read/28386183/establishment-of-preliminary-regulatory-network-of-trpv1-and-related-cytokines
#13
Jianhua Zhang, Zheng Zhou, Ning Zhang, Wenwen Jin, Yafeng Ren, Chuanliang Chen
Our purpose was to investigate the regulatory mechanism of TRPV1 and related cytokines on children bronchial asthma. TRPV1 mRNA level and two SNP genotypes of children in case group and control group were detected by real-time quantitative PCR. Western blot and ELISA were used to measure the levels of cytokines like IgE, IL-2, etc. Their correlations were analyzed by Logistic regression and KEGG analysis. Moreover, tertiary structure of protein and miRNA binding sites were also predicted by online tools. Case group was obviously different from control group in TRPV1 mRNA level, the two SNP genotypes distribution and the related cytokines levels...
March 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28383034/pulmonary-microrna-profiles-identify-involvement-of-creb1-and-sec14l3-in-bronchial-epithelial-changes-in-allergic-asthma
#14
Sabine Bartel, Nikola Schulz, Francesca Alessandrini, Andrea C Schamberger, Philipp Pagel, Fabian J Theis, Katrin Milger, Elfriede Noessner, Stephen M Stick, Anthony Kicic, Oliver Eickelberg, Robert J Freishtat, Susanne Krauss-Etschmann
Asthma is highly prevalent, but current therapies cannot influence the chronic course of the disease. It is thus important to understand underlying early molecular events. In this study, we aimed to use microRNAs (miRNAs) - which are critical regulators of signaling cascades - to identify so far uncharacterized asthma pathogenesis pathways. Therefore, deregulation of miRNAs was assessed in whole lungs from mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI). In silico predicted target genes were confirmed in reporter assays and in house-dust-mite (HDM) induced AAI and primary human bronchial epithelial cells (NHBE) cultured at the air-liquid interface...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28379462/human-metapneumovirus-infection-in-chronic-obstructive-pulmonary-disease-impact-of-glucocorticosteroids-and-interferon
#15
Keiko Kan-O, Ruben Ramirez, Martin I MacDonald, Michael Rolph, Penny A Rudd, Kirsten M Spann, Suresh Mahalingam, Philip G Bardin, Belinda J Thomas
Background.: Human metapneumovirus (hMPV) infection is implicated in exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Research into the pathogenesis of infection is restricted to animal models and information about hMPV replication and inflammatory and immune responses in human disease is limited. Methods.: Human primary bronchial epithelial cells (PBEC) from healthy, asthmatic and COPD subjects were infected with hMPV, with or without glucocorticosteroids (GCS) exposure...
April 4, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28378957/asthma-and-gastro-oesophageal-reflux-disease-a-multidisciplinary-point-of-view
#16
Paolo Solidoro, Filippo Patrucco, Sharmila Fagoonee, Rinaldo Pellicano
Asthma and gastro-oesophageal reflux (GORD) are widespread and potentially coexisting diseases. Incidence and prevalence of concomitant asthma and GORD are highly variable among studies. This is mainly due to the heterogeneity of study designs. To explain a potential link, it has been proposed some pathophysiological anomaly such as the altered pressure gradient between thorax and abdomen, the parasympathethic reflex, the hightened bronchial reactivity and chemical effects of microaspired gastric juice. An accurate diagnosis of asthma and GORD are pivotal in order to lead effective treatment and to reach a significant positive outcome, in terms of quality of life and respiratory function amelioration...
April 4, 2017: Minerva Medica
https://www.readbyqxmd.com/read/28378503/il-5-stimulated-eosinophils-adherent-to-periostin-undergo-stereotypic-morphological-changes-and-adam8-dependent-migration
#17
Mats W Johansson, Manav Khanna, Valeriu Bortnov, Douglas S Annis, Christopher L Nguyen, Deane F Mosher
BACKGROUND: IL-5 causes suspended eosinophils to polarize with filamentous (F)-actin and granules at one pole and the nucleus in a specialized uropod, the "nucleopod", which is capped with P-selectin glycoprotein ligand-1 (PSGL-1). IL-5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators. OBJECTIVE: Determine how the polarized morphology evolves to foster migration of IL-5-stimulated eosinophils on a surface coated with periostin...
April 4, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28371335/genetic-susceptibility-to-severe-asthma-with-fungal-sensitization
#18
N L Overton, A Simpson, P Bowyer, D W Denning
Severe asthma is problematic and its pathogenesis poorly understood. Fungal sensitization is common, and many patients with severe asthma with fungal sensitization (SAFS), used to denote this subgroup of asthma, respond to antifungal therapy. We have investigated 325 haplotype-tagging SNPs in 22 candidate genes previously associated with aspergillosis in patients with SAFS, with comparisons in atopic asthmatics and healthy control patients, of whom 47 SAFS, 279 healthy and 152 atopic asthmatic subjects were genotyped successfully...
March 31, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28366474/inflammatory-disorders-associated-with-allergy-overview-of-immunopathogenesis-and-implications-for-treatment
#19
REVIEW
Jonathan Corren
A number of chronic inflammatory diseases are associated with IgE-mediated immunologic hypersensitivity, including atopic dermatitis, chronic rhinosinusitis, and asthma. Pathogenetic studies of well-characterized patient groups has allowed investigators to more precisely define the molecular pathways involved in these diseases. Specific cytokines and chemokines, as well as other unique proteins, have now been identified in each of these common disorders and a number of medications are currently in development for inhibiting their actions...
May 2017: Immunology and Allergy Clinics of North America
https://www.readbyqxmd.com/read/28358425/ormdl3-is-associated-with-airway-remodeling-in-asthma-via-the-erk-mmp-9-pathway
#20
Fei Yu, Yan Sun, Jiachen Yu, Zhen Ding, Jinrong Wang, Lanyun Zhang, Tiejing Zhang, Yun Bai, Yulin Wang
ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) has been previously implicated in asthma pathogenesis, its effect on airway remodeling remains to be elucidated. The present study examined the expression levels of ORMDL3 in a mouse model of asthma. Mice were divided into three groups: Asthmatic model (n=10), budesonide‑treated (n=10) and a control group (n=8). Asthma was induced by sensitization with ovalbumin (OVA) and aluminum hydroxide on day 1, 7 and 14. Subsequently mice were exposed to OVA three times per week from day 28...
March 30, 2017: Molecular Medicine Reports
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