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Glucocorticoid asthma

Gessica Marchini, Silvia Carnevali, Fabrizio Facchinetti
Cigarette smokers with asthma and chronic obstructive pulmonary disease (COPD) are less responsive to glucocorticoids (GCs). The anti-inflammatory action of GCs depends also on their ability to transactivate genes such as GC-induced leucine zipper (GILZ). We investigated the effects of aqueous cigarette smoke extract (CSE) on GILZ transactivation evoked by 17-beclomethasone monopropionate (BMP) or fluticasone propionate (FP) in the presence or absence of the long acting β2-adrenoceptor agonist (LABA) bronchodilator formoterol or salmeterol in human primary cultures of human bronchial smooth muscle cells (HBSMC)...
February 9, 2019: European Journal of Pharmacology
Huojun Zhang, Qian Liu, Luxia Kong, Shuyun Xu
AIMS: To investigate whether mucin 1 (MUC1) downregulation reduced the sensitivity of tumor necrosis factor-alpha (TNF-α)-induced bronchial epithelial cells to glucocorticoid-mediated necroptosis and explore the underlying mechanisms. MAIN METHODS: The human lung bronchial epithelial cell line (16HBE) was transfected with small interfering RNA (siRNA) against MUC1 and then stimulated by TNF-α, where some cells were pretreated with dexamethasone. Flow cytometry was performed to analyze necroptosis in 16HBE cells, and western blot analysis was used to detect protein expression levels of MUC1, glucocorticoid receptor (GR)α, GRβ, NF-κB p65, phospho-p65 (p-p65), and histone deacetylase-2 (HDAC2)...
February 6, 2019: Life Sciences
Stacey M Leventhal, Debora Lim, Tajia L Green, Anna E Cantrell, Kiho Cho, David G Greenhalgh
BACKGROUND: Glucocorticoids are commonly used in the clinical setting for their potent anti-inflammatory effects; however, significant variations in response to treatment have been demonstrated. Although the underlying mechanisms have yet to be fully understood, this variable response may be a result of alterations in human glucocorticoid receptor (hGR) expression and function. In addition to hGRα, the biologically active isoform, a screening of current databases and publications revealed five alternative splice isoforms and hundreds of variants that have been reported to date...
February 8, 2019: BMC Genetics
Mahmoud M Mostafa, Christopher F Rider, Suharsh Shah, Suzanne L Traves, Paul M K Gordon, Anna Miller-Larsson, Richard Leigh, Robert Newton
BACKGROUND: Glucocorticoids act on the glucocorticoid receptor (GR; NR3C1) to resolve inflammation and, as inhaled corticosteroids (ICS), are the cornerstone of treatment for asthma. However, reduced efficacy in severe disease or exacerbations indicates a need to improve ICS actions. METHODS: Glucocorticoid-driven transcriptomes were compared using PrimeView microarrays between primary human bronchial epithelial (HBE) cells and the model cell lines, pulmonary type II A549 and bronchial epithelial BEAS-2B cells...
January 31, 2019: BMC Medical Genomics
Mengyuan Kan, Cynthia Koziol-White, Maya Shumyatcher, Martin Johnson, William Jester, Reynold A Panettieri, Blanca E Himes
Glucocorticoids, commonly used asthma controller medications, decrease symptoms in most patients, but some remain symptomatic despite high dose treatment. The physiological basis underlying glucocorticoid response, especially among asthma patients with severe, refractory disease is not fully understood. We sought to identify differences between fatal asthma and non-asthma donor-derived airway smooth muscle (ASM) cell transcriptomic response to glucocorticoid exposure, and to compare ASM-specific changes to those of other cell types...
January 29, 2019: American Journal of Respiratory Cell and Molecular Biology
Amira Ali Ramadan, Jonathan M Gaffin, Elliot Israel, Wanda Phipatanakul
Corticosteroids are the most effective treatment for asthma; inhaled corticosteroids (ICSs) are the first-line treatment for children and adults with persistent symptoms. ICSs are associated with significant improvements in lung function. The anti-inflammatory effects of corticosteroids are mediated by both genomic and nongenomic factors. Variation in the response to corticosteroids has been observed. Patient characteristics, biomarkers, and genetic features may be used to predict response to ICSs. The existence of multiple mechanisms underlying glucocorticoid insensitivity raises the possibility that this might indeed reflect different diseases with a common phenotype...
March 2019: Clinics in Chest Medicine
B Liao, M Zeng, J X Liu
Objective: The purposes of present study were to explore the relative factors affecting treatment outcomes of chronic rhinosinusitis(CRS),and investigated the clinical manifestation changes of CRS patients after post-operative treatment of oral glucocorticoid. Method: Forty-eight CRS subjects including 14 illness un-controlled group, and 34 illness controlled group were enrolled, and peripheral blood leukocytes, eosinophils, neutrophils, mononuclear cells, lymphocytes were detected and clinical features comprised of VAS, endoscopy and CT scan scores were recorded; 20 days'oral glucocorticoid was prescribed to the patients in illness un-controlled group and the data described above were analyzed...
January 2019: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
Arthur R Galbraith, Donna E Seabloom, Beverly R Wuertz, Jennifer D Antonides, Vernon E Steele, Lee W Wattenberg, Frank G Ondrey
Nicotinamide, the amide form of vitamin B3, and budesonide, a synthetic glucocorticoid used in the treatment of asthma, were evaluated to determine their individual and combinational chemopreventive efficacy on benzo(a)pyrene induced lung tumors in female A/J mice. Nicotinamide fed at a dietary concentration of 0.75% significantly inhibited tumor multiplicity. Nicotinamide by aerosol inhalation at doses up to 15 mg/kg/day did not result in a statistically significant reduction in tumor multiplicity. Finally, dietary nicotinamide was administered with aerosol budesonide and tumor multiplicity reduced by 90% at 1 week and 49% at 8 weeks post last carcinogen dose...
January 3, 2019: Cancer Prevention Research
Elizabeth H Mann, Leona Gabryšová, Paul E Pfeffer, Anne O'Garra, Catherine M Hawrylowicz
Glucocorticoids are known to increase production of the anti-inflammatory cytokine IL-10, and this action is associated with their clinical efficacy in asthmatics. However, glucocorticoids also enhance the synthesis of IL-17A by PBMCs, which, in excess, is associated with increased asthma severity and glucocorticoid-refractory disease. In this study, we show that the glucocorticoid dexamethasone significantly increased IL-10 production by human memory CD4+ T cells from healthy donors, as assessed by intracellular cytokine staining...
December 31, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Haipeng Bao, Dongxu Si, Longxia Gao, Huizhuo Sun, Qi Shi, Yue Yan, Dashzeveg Damchaaperenlei, Chunlei Li, MingXia Yu, Youlin Li
BACKGROUND: Allergic rhinitis is a major chronic inflammatory disease of the respiratory tract. A large number of epidemiological investigations have shown that the prevalence of allergic rhinitis (AR) is increasing, resulting in a large burden of disease. Desensitizing drugs such as nasal glucocorticoids and antihistamines are commonly used to treat allergic rhinitis, but this method has a long treatment period and is prone to repeated attacks, and there are certain adverse reactions...
December 2018: Medicine (Baltimore)
Rodney D Britt, Michael A Thompson, Sarah Sasse, Christina M Pabelick, Anthony N Gerber, Y S Prakash
Corticosteroids (CSs) are commonly used to manage wheezing and asthma in pediatric populations. Although corticosteroids are effective in alleviating airway diseases, some children with more moderate-severe asthma phenotypes show CS resistance and exhibit significant airflow obstruction, persistent inflammation, and more frequent exacerbations. Previous studies have demonstrated that Th1 cytokines, such as TNF-α and IFN-γ, promote CS resistance in adult human airway smooth muscle (ASM). In the present study, using a human fetal ASM cell model, we tested the hypothesis that TNF-α/IFN-γ induces CS resistance...
January 1, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
Alisa M Gorbacheva, Dmitry V Kuprash, Nikita A Mitkin
Interleukin 33 (IL-33) is a cytokine constitutively expressed by various cells of barrier tissues that contribute to the development of inflammatory immune responses. According to its function as an alarmin secreted by lung and airway epithelium, IL-33 plays a significant role in pathogenesis of allergic disorders. IL-33 is strongly involved in the pathogenesis of asthma, anaphylaxis, allergy and dermatitis, and genetic variations in IL33 locus are associated with increased susceptibility to asthma. Genome-wide association studies have identified risk "T" allele of the single-nucleotide polymorphism rs4742170 located in putative IL33 enhancer area as susceptible variant for development of specific wheezing phenotype in early childhood...
December 9, 2018: International Journal of Molecular Sciences
Carlo C Campa, Rangel L Silva, Jean P Margaria, Tracey Pirali, Matheus S Mattos, Lucas R Kraemer, Diego C Reis, Giorgio Grosa, Francesca Copperi, Eduardo M Dalmarco, Roberto C P Lima-Júnior, Silvio Aprile, Valentina Sala, Federica Dal Bello, Douglas Silva Prado, Jose Carlos Alves-Filho, Claudio Medana, Geovanni D Cassali, Gian Cesare Tron, Mauro M Teixeira, Elisa Ciraolo, Remo C Russo, Emilio Hirsch
PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action...
December 12, 2018: Nature Communications
Cheng-Ping Hu, Qiu-Fen Xun, Xiao-Zhao Li, Xin-Yue Hu, Ling Qin, Ruo-Xi He, Jun-Tao Feng
Background: Glucocorticoid (GC) is the first-line therapy for asthma, but some asthmatics are insensitive to it. Glucocorticoid-induced transcript 1 gene (GLCCI1) is reported to be associated with GCs efficiency in asthmatics, while its exact mechanism remains unknown. Methods: A total of 30 asthmatic patients received fluticasone propionate for 12 weeks. Forced expiratory volume in 1 s (FEV1 ) and GLCCI1 expression were detected. Asthma model was constructed in wild-type and GLCCI1 knockout (GLCCI1-/- ) mice...
December 5, 2018: Chinese Medical Journal
Reynold A Panettieri, Dedmer Schaafsma, Yassine Amrani, Cynthia Koziol-White, Rennolds Ostrom, Omar Tliba
Glucocorticoid (GC) anti-inflammatory effects generally require a prolonged onset of action and involve genomic processes. Because of the rapidity of some of the GC effects, however, the concept that non-genomic actions may contribute to GC mechanisms of action has arisen. While the mechanisms have not been completely elucidated, the non-genomic effects may play a role in the management of inflammatory diseases. For instance, we recently reported that GCs 'rapidly' enhanced the effects of bronchodilators, agents used in the treatment of allergic asthma...
November 26, 2018: Trends in Pharmacological Sciences
Ledina Imami, Sarah C E Stanton, Samuele Zilioli, Erin T Tobin, Allison K Farrell, Francesca Luca, Richard B Slatcher
Self-disclosure and perceived responsiveness are important building blocks of social relationships that have long-lasting consequences for health and well-being. However, the conditions under which self-disclosure and responsiveness are likely to benefit health, and how early in life these benefits arise, remain unclear. Among 141 youth (aged 10-17) with asthma, we investigated how average daily levels of self-disclosure and responsiveness are linked to positive and negative affect and the expression of the glucocorticoid receptor gene NR3C1, a marker of improved regulation of stress physiology and immune functioning...
November 28, 2018: Personality & Social Psychology Bulletin
Sina A Gharib, Ryan S McMahan, William E Eddy, Matthew E Long, William C Parks, Moira L Aitken, Anne M Manicone
BACKGROUND: Macrophage plasticity allows cells to adopt different phenotypes, a property with important implications in disorders such as cystic fibrosis (CF) and asthma. OBJECTIVE: We sought to examine the transcriptional and functional significance of macrophage repolarization from an M1 to an M2 phenotype and assess the role of a common human genetic disorder (CF) and a prototypical allergic disease (asthma) in this transformation. METHODS: Monocyte-derived macrophages were collected from healthy subjects and patients with CF and polarized to an M2 state by using IL-4, IL-10, glucocorticoids, apoptotic PMNs, or azithromycin...
November 14, 2018: Journal of Allergy and Clinical Immunology
Yann Nguyen, Loïc Guillevin
Eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is a systemic necrotizing vasculitis of small- and medium-size vessels, characterized by asthma and blood eosinophilia. EGPA typically occurs in patients with preexisting asthma, and involves the skin, lungs, and peripheral nerves. Poor-prognosis factors (i.e., involvement(s) of the gastrointestinal tract, heart, and/or kidney) have been assessed with the Five-Factor Score (FFS). One-third of the patients have anti-myeloperoxidase antineutrophil cytoplasm antibodies, and their presence seems to differentiate between two phenotypes, with different clinical characteristics and prognoses...
August 2018: Seminars in Respiratory and Critical Care Medicine
Ying Tang, Caiyun Zhang, Zhigang Zhang, Jinhui Tian
OBJECTIVE: To determine the efficacy and safety of current maintenance therapies consisting of different regimens of long-acting β2-agonists (LABA) with inhaled corticosteroids (ICS) in patients with asthma. METHODS: A network meta-analysis (NMA) was conducted after a comprehensive search for relevant studies in the PubMed, Cochrane Library, and Embase databases up to January 1, 2017. Randomized clinical trials comparing LABA combined with ICS in patients with asthma were selected...
October 25, 2018: Journal of Asthma: Official Journal of the Association for the Care of Asthma
X Shi, R H Qiu, Z D Lai, M Z Qiu, S S Wei, J X Xie, X X Zhang, F G Deng, J Li, Y Y Gu, L Dai, Q L Zhang, N F Zhang, S Y Li, R C Chen
Objective: To improve the clinical recognition of eosinophilic granulomatosis with polyangiitis(EGPA) in clinical manifestations, diagnosis and treatment. Methods: The clinical manifestations, pathological characteristic, imaging manifestations, diagnosis and the therapy of three patients with EGPA were presented. Results: These 3 patients had asthma-like symptoms and extrapulmonary manifestations of systemic vasculitis. They were 20, 40 and 44 years old. All of them were female.They denied exposure or contact...
October 12, 2018: Chinese Journal of Tuberculosis and Respiratory Diseases
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