Dissertations / Theses on the topic 'Glucocorticoid resistance in Asthma'
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Matthews, John Graham. "The differential effects of glucocorticords in glucocorticoid-dependent asthma, glucocorticoid-resistant asthma and healthy subjects." Thesis, Imperial College London, 2006. http://hdl.handle.net/10044/1/8204.
Full textLane, Stephen John. "Mechanism of glucocorticoid resistance in chronic bronchial asthma." Thesis, King's College London (University of London), 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300513.
Full textLoke, Tuck-Kay. "The cellular & molecular pathology of glucocorticoid resistant asthma." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430825.
Full textYAMAMOTO, MASAHIRO, YUTAKA OISO, MITSUYA MORIKAWA, SATOSHI KAKIYA, HISASHI YOKOI, ATSUSHI SUZUKI, and AKITOSHI KAWAKUBO. "A CASE OF PRIMARY GLUCOCORTICOID RESISTANCE." Nagoya University School of Medicine, 1995. http://hdl.handle.net/2237/16090.
Full textHinds, Terry D. Jr. "Protein Phosphatase 5 and Glucocorticoid Receptor beta in Glucocorticoid Resistance and Lipogenesis." University of Toledo Health Science Campus / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=mco1289929592.
Full textJaffuel, Dany. "Corticothérapie et asthme : étude cellulaire de la transrépression du facteur de transcription AP-1 par le récepteur aux glucocorticoi͏̈des." Montpellier 1, 1997. http://www.theses.fr/1997MON11104.
Full textGaffey, Kate. "Glucocorticoid resistance in COPD : the role of p38 MAPK." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/glucocorticoid-resistance-in-copd-the-role-of-p38-mapk(9c60954b-f891-4f8b-8004-825e6d173503).html.
Full textKmyta, V. "Bcli polymorphism of glucocorticoid receptor gene in patients with bronchial asthma and obesity." Thesis, Sumy State University, 2015. http://essuir.sumdu.edu.ua/handle/123456789/40552.
Full textButler, C. A. "Mechanisms of steroid resistance in therapy resistant asthma." Thesis, Queen's University Belfast, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546017.
Full textNixon, Mark. "Interactions between glucocorticoid metabolism and inflammation in obesity and insulin resistance." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5593.
Full textStark, Jennifer L. "Social Stress and the induction of Glucocorticoid resistance in male mice /." The Ohio State University, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=osu1486401895208126.
Full textTrebble, Peter. "Glucocorticoid receptor function : new insights from genetic and chemical biology approaches." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/glucocorticoid-receptor-function-new-insights-from-genetic-and-chemical-biology-approaches(b55c612b-eda1-4908-a0df-ec916f03ade2).html.
Full textLynch, James Thomas. "Molecular mechanisms conferring resistance/sensitivity to glucocorticoid-induced apoptosis during cytotoxic stress." Thesis, University of Manchester, 2009. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:151882.
Full textDhanda, Ashwin Deep. "Mechanisms of glucocorticoid resistance in inflammatory diseases of the gut and liver." Thesis, University of Bristol, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665487.
Full textStrand, Victoria. "Effects of nitrogen dioxide on airway responsiveness in allergic asthma /." Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980821stra.
Full textNicholson, Lindsay. "The role of NFκB in glucocorticoid resistance in childhood acute lymphoblastic leukaemia (ALL)." Thesis, University of Newcastle Upon Tyne, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.493230.
Full textHuang, Edmond Y. Mathews Suresh T. "A novel role for fetuin-A in the pathophysiology of glucocorticoid-mediated insulin resistance." Auburn, Ala, 2008. http://repo.lib.auburn.edu/EtdRoot/2008/SPRING/Nutrition_and_Food_Science/Thesis/Huang_Edmond_42.pdf.
Full textChachi, Latifa. "New insight into the molecular mechanisms of corticosteroid resistance in asthma." Thesis, University of Leicester, 2014. http://hdl.handle.net/2381/29242.
Full textSchoenle, Laura Ann. "Coping with Chronic Infection: The Role of Glucocorticoid Hormones in Mediating Resistance and Tolerance to Parasites." Diss., Virginia Tech, 2017. http://hdl.handle.net/10919/86535.
Full textPh. D.
Riebold, Mathias. "Investigations on the role of Hsp90 in the pathogenic glucocorticoid resistance of corticotroph pituitary adenomas." Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-177888.
Full textHow, Stephen Christopher. "Effect of acute and chronic pressure-threshold inspiratory muscle training on upper and lower airway function." Thesis, Brunel University, 2010. http://bura.brunel.ac.uk/handle/2438/5517.
Full textMcBeth, Lucien Reiter. "Glucocorticoid Receptor beta Increases the Migration of Human Urothelial Carcinoma Cells." University of Toledo Health Science Campus / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=mco1467031531.
Full textLivingston, Eric. "Effect of environmental factors (smoking and allergen exposure) on corticosteroid resistance in asthma." Thesis, University of Glasgow, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433613.
Full textLowe, Alexander Paul. "The role of viral and bacterial infections in asthma exacerbations and corticosteroid resistance." Thesis, Cardiff University, 2013. http://orca.cf.ac.uk/47342/.
Full textFlood, Lars. "Glucocorticosteroid therapy and steroid resistance in inflammatory bowel disease /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-020-6/.
Full textRiebold, Mathias [Verfasser], and Mathias [Akademischer Betreuer] Schmidt. "Investigations on the role of Hsp90 in the pathogenic glucocorticoid resistance of corticotroph pituitary adenomas / Mathias Riebold. Betreuer: Mathias Schmidt." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2014. http://d-nb.info/106561070X/34.
Full textMarchica, Cinzia Loreta 1984. "Allergen-induced asthma is decreased in decorin-deficient mice." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116096.
Full textGallagher, Kayleigh M. "Identification of ESRRB and SOX2 as novel mediators of the glucocorticoid response in acute lymphoblastic leukemia." eScholarship@UMMS, 2020. https://escholarship.umassmed.edu/gsbs_diss/1093.
Full textGoodrich, Geoffrey G. "Detoxification gene polymorphisms, patient demographics, environmental exposures and potential relationships with childhood asthma cross-sectional case study /." abstract and full text PDF (free order & download UNR users only), 2008. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3326205.
Full textBarck, Charlotte. "Airway responses to NO₂ and allergen in asthmatics /." Stockholm : Karolinska University Press, 2005. http://diss.kib.ki.se/2005/91-7140-273-X/.
Full textLê, Tuan Thành. "Lung function by plethysmography : a new method in Vietnam for asthma diagnosis." Thesis, Université de Lorraine, 2015. http://www.theses.fr/2015LORR0341/document.
Full textDespite the increasing prevalence of asthma in Viet Nam, the country has limited means for respiratory function testing. A previous study using the forced oscillation technique suggested lower respiratory resistance between French and Vietnamese children at 10 years but not 6 years of age. If the hypothesis of a significant ethnic difference in airway caliber is correct, then similar differences should exist at adult age. To test the hypothesis, a plethysmographic study was set up to measure airway resistance and specific airway resistance in healthy young adults in France and Viet Nam. We took advantage of the study to provide reference values for lung volume in these populations. Airway resistance is significantly larger in Vietnamese than in Caucasians but there is no difference in specific airway resistance. Altogether the study does not support the consequence of a putative ethnic difference in childhood airway caliber on airway resistance normalized for lung volume at adult age. The standing height is the best predictor of the total lung capacity, while ethnicity is an important predictor of vital capacity and of the residual volume to total lung capacity ratio. This is the first study which provides reference values for airway resistance, specific airway resistance and lung volumes by plethysmography in healthy young Vietnamese adults. Plethysmography was validated in the north of Viet Nam, and the study allowed initiating a young working group on asthma diagnosis in Vietnam
Calixto, Marina Ciarallo 1980. "Efeito da ativação da AMPK na exacerbação da inflamação pulmonar alérgica em camundongos obesos." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308911.
Full textTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-21T14:09:45Z (GMT). No. of bitstreams: 1 Calixto_MarinaCiarallo_D.pdf: 2454146 bytes, checksum: 3f9d2c9797c668d719c59ae5fd3f277f (MD5) Previous issue date: 2012
Resumo: A obesidade e a asma são doenças prevalentes e crescentes, e ambas têm impacto significativo na saúde pública mundial. O aumento simultâneo da prevalência da asma e da obesidade tem levado investigadores a sugerir que a obesidade possa ser um fator importante no desenvolvimento da asma, ou até piorar um quadro de asma pré-existente. Numerosos estudos populacionais conduzidos em todo o mundo indicam que a prevalência de asma é maior em indivíduos obesos versus magros. Além disso, diversos estudos prospectivos, tanto em adultos quanto em crianças, indicam que o risco relativo da incidência de asma aumenta com o índice de massa corporal (IMC). A obesidade também piora o controle medicamentoso da asma e a gravidade desta doença. Recentemente, diversos dados emergiram indicando que a inflamação associada à obesidade pode aumentar a propensão para o desenvolvimento de asma. Acredita-se que a resistência à insulina associada à obesidade desempenha importante papel no desenvolvimento da asma, explicando, ao menos em parte, a associação da asma com obesidade. Relatos recentes indicam uma alta prevalência de resistência à insulina em pacientes obesos e asmáticos versus obesos não asmáticos, sugerindo que a resistência à insulina possa contribuir com este fenótipo. Baseado nestas informações, o objetivo deste trabalho foi verificar se doenças metabólicas associadas à obesidade, tal como a resistência à insulina, podem estar envolvidas na exacerbação da asma associada à obesidade. No presente estudo observamos que o tratamento de camundongos obesos com metformina corrige a resistência à ação sistêmica da insulina. Além disso, metformina normaliza o trânsito dos eosinófilos da medula óssea até o lúmen em animais obesos e desafiados com OVA. Essa normalização parece ser mediada pela ativação da AMPK no pulmão e diminuição das concentrações de TNF-? e NOx no LBA e inibição da expressão de iNOS induzida pelo fator de transcrição NF-?B no pulmão. Além disso, ao normalizar o tráfego de eosinófilos da região peribronquiolar para a luz das vias aéreas, o tratamento com metformina induz concomitante diminuição do acúmulo de eosinófilos na medula óssea devido à regulação positiva da expressão de moléculas de adesão VLA-4 e Mac-1 na superfície das células e posterior aumento da resposta adesiva à ICAM-1 e VCAM-1. Os resultados descritos neste estudo parecem confirmar a hipótese que a resistência à insulina, resultante da obesidade, medeia a exacerbação da resposta inflamatória pulmonar observada em animais obesos. Dessa forma, ao corrigir a resistência à insulina sistêmica através da ativação da AMPK, camundongos sensibilizados obesos aceleram o início do processo de resolução da inflamação pulmonar alérgica
Abstract: Obesity and asthma are prevalent and increasing diseases, and both have significant impact on global public health. The increase in prevalence of asthma and obesity has led researchers to suggest that obesity may be an important factor in the development of asthma, or even worse the pre-existing asthma. Numerous populational studies conducted around the world indicate that the prevalence of asthma is higher in obese versus lean person. In addition, several prospective studies, both in adults and in children, indicate that the relative risk of incident asthma increases with body mass index (BMI). Obesity also worsens the drug therapy of asthma and the severity of this disease. Recently, several data emerged showing that the inflammation associated with obesity increase the propensity for development of asthma. It is believed that insulin resistance associated with obesity plays an important role in the development of asthma, explaining, at least in part, asthma associated with obesity. Recent reports indicate a high prevalence of insulin resistance in obese asthmatics versus obese non-asthmatics patients, suggesting that insulin resistance may contribute to this phenotype. Based on this information, the purpose of this study was to determine whether metabolic diseases associated with obesity such as insulin resistance, are involved in asthma exacerbation associated with obesity. In the present study we observed that obese mice treated with metformin, impairs the resistantance to the systemic action of insulin. Furthermore, in obese mice challend with OVA, metformin normalizes the transit of eosinophils from bone marrow to the lung lumen. This normalization is mediated by AMPK activation in the lung, as well as decreased concentrations of TNF-? and nitrite and nitrate in BAL fluid accompanied by the inhibition of NF-?B induced iNOS expression in the lung. Furthermore, by normalizing the eosinophils trafficking from peribronchiolar region to airway lumen, metformin treatment induces concomitant reduction in the accumulation of eosinophils in bone marrow through the upregulation of adhesion molecules VLA-4 and Mac-1 on cell surface and subsequent increase in the adhesive response to plates coated with ICAM-1 and VCAM-1. Our data seem to confirm the hypothesis that insulin resistance resulting from obesity mediates the exacerbation of airway inflammation in high fat-diet mice. Thus, by normalizing the systemic insulin resistance through the atictivation of AMPK, obese sensitized mice progress to resolution of allergic airway inflammation
Doutorado
Farmacologia
Doutora em Farmacologia
Dalle, Heloïse. "Rôle du récepteur adipocytaire des glucocorticoïdes dans les troubles métaboliques liés à un traitement par la corticostérone Adipocyte glucocorticoid receptor deficiency promotes adipose tissue expandability and improves the metabolic profile under corticosterone exposure Glucocorticoid-induced insulin resistance is related to macrophage visceral adipose tissue infiltration." Thesis, Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2019SORUS065.pdf.
Full textGlucocorticoids (GC) are among the medications most commonly prescribed because of their anti-inflammatory and immunosuppressive properties. However, high doses can lead to side effects including GC-induced diabetes and lipodystrophy. The contribution of adipocyte glucocorticoid receptor (GR) in the molecular mechanisms of these complications remains to be investigated. The goal of this study was to determine the precise role of the GR in the development of insulin-resistance and associated metabolic dysregulations in a context of hypercorticism. For this purpose, we have generated an inducible mouse model of GR invalidation specifically in the adipocyte (AdipoGR-KO), which was submitted to a four-week corticosterone treatment. Metabolic phenotype of AdipoGR-KO mice showed an increase of fat mass associated with a paradoxical improvement of glucose tolerance, insulin sensitivity, lipid profile and liver steatosis compared to WT mice. Preferential and beneficial fat storage in adipose tissue prompted us to investigate the mechanisms involved in the excessive development of adipose tissue, in particular the vascularization. Surprisingly, our results showed a higher development of capillary network in fat pads of AdipoGR-KO mice, associated with a strong induction of the angiogenic factor VEGF-A and its transcriptional regulator HIF-1α. Thus, we show for the first time that GR could be a limiting factor of adipose tissue expansion through the inhibition of the angiogenic process
Sribanditmongkol, Vorachai. "Effects of Psychological Stress on Glucocorticoid Sensitivity of Inflammatory Response to Influenza Vaccine Challenge in Healthy Military College Students." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366195257.
Full textKaraki, Soumaya. "Effets immunorégulateurs de la protéine GILZ (Glucocorticoid-induced leucine Zipper) sur la fonction des cellules dendritiques dans la réponse immunitaire allergique : étude Clinique et expérimentale." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00923138.
Full textSimões, Joana de Sousa Azevedo. "Contribution to the discriminant power of some of the variables involved in the staging of severe equine asthma syndrome." Doctoral thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2020. http://hdl.handle.net/10400.5/19939.
Full textSevere Equine Asthma Syndrome (EAS) is a highly prevalent, chronic and recurrent respiratory disease which appears to be related to equine domestication. Due to its insidious nature, treatment may sometimes be frustrating and severe economic loses occur. Genetically susceptible individuals develop airway inflammation, hyperresponsiveness and obstruction when exposed to environments with high concentrations of respirable dust particles, which include mould spores, mites, endotoxins, pollen and other antigenic materials. These hazardous respirable dust concentrations are usually found in traditional equine housing systems, while lower concentrations tend to be present in outdoor systems (pasture). The management of severe EAS essentially requires environmental control to ensure improvement of lung function and in some cases medical treatment with corticosteroids and bronchodilators to ameliorate the clinical signs of airway inflammation and bronchospasm. Considering the clinical importance of this syndrome, the dissertation focuses on further contributing to scientific knowledge of severe EAS. As such, we investigated the influence of lung function tests on the diagnosis and staging of the disease and developed a staging method using only portable equipment, which has the potential of being used in equine ambulatory practice. We also investigated the relation between severe EAS and resistance to gastrointestinal parasites, which had not been, to the author’s knowledge, previously reported in the Lusitano breed horses. This association has been reported in other equine breeds with severe EAS or with other multiple hypersensitivities (MHS). Lastly, because allergen avoidance is fundamental for the remission of severe EAS we examined owner compliance to a set of recommended guidelines for environmental management.
RESUMO - A síndrome de asma equina (SAE) grave é uma doença respiratória crónica, recorrente e altamente prevalente em animais adultos, estando associada à domesticação dos equinos. Devido à sua natureza insidiosa, o tratamento é muitas vezes frustrante, originando perdas económicas significantes. Quando expostos a ambientes com elevadas concentrações de partículas respiráveis, tais como esporos de fungos, ácaros, endotoxinas, pólen e outras partículas antigénicas, os animais geneticamente suscetíveis desenvolvem inflamação, hiper-reactividade e obstrução das vias aéreas. As concentrações de partículas respiráveis elevadas encontram-se normalmente presentes em sistemas de estabulação de equinos tradicionais, enquanto que em sistemas em extensivo (pastagem) estas concentrações tendem a ser menores. Assim, no maneio da SAE grave é essencial o controlo ambiental de modo a assegurar a melhoria da função pulmonar e em alguns casos o tratamento médico com corticosteroides e broncodilatadores para reduzir os sinais clínicos de inflamação das vias aéreas e broncospasmo. Tendo em conta a importância clínica desta síndrome, esta dissertação tem por objetivo contribuir para o conhecimento científico da SAE grave. Assim sendo, investigámos a influencia dos testes de função pulmonar no diagnóstico e estadiamento da doença e desenvolvemos um método de estadiamento, utilizando apenas equipamento portátil, o qual poderá ser utilizado na clínica em regime de ambulatório. Ainda, investigámos a relação entre SAE grave e a resistência a parasitas gastrointestinais, a qual até à data ainda não havia sido reportada em cavalos Puro Sangue Lusitanos. Esta associação foi, contudo, descrita em equinos de outras raças diagnosticados com SAE grave ou outras hipersensibilidades múltiplas. Por fim, considerando que a remoção de aeroalérgenos é fundamental para a remissão da SAE grave, procurámos avaliar a complacência dos donos dos animais asmáticos a um conjunto de recomendações de maneio ambiental.
CIISA through the project INOV CIISA 8.
N/A
Balan, Ioan Iulia-Cristina. "Diagnostic de l'asthme chez l'enfant par la réversibilité de l'obstruction bronchique." Thesis, Université de Lorraine, 2014. http://www.theses.fr/2014LORR0132/document.
Full textShorter lung function testing methods are needed in young asthmatic children, requiring minimal cooperation, performed in spontaneous breathing, without anaesthesia. Such methods are measurement of respiratory impedance by forced oscillations technique, measurement of specific airway resistance by plethysmography or capnography, measurement of CO2 concentration in expired air. The main objective of this work was to improve pediatric asthma diagnosis by using clinical and experimental studies. A study including asthmatic and control children showed that the specificity of resistance was improved in expiration compared to inspiration due to the fact that the glottis closure during expiration was proportional to the degree of airway obstruction. Another clinical study demonstrated that asthma diagnosis was improved by computation of respiratory admittance response to a bronchodilator because this computation is not affected by upper airways artifact. A study showed that specific airway resistance measured during spontaneous breathing was overestimated compared to panting metthod. Capnography is a non invasive technique. The shape of the expired CO2 time course is altered by the non homogenous distribution of ventilation resulting from bronchoconstriction. But its clinical usefulness in young children may be limited by the relatively high respiratory rate. An experimental study was conducted in rabbits to validate capnogram shape indices at different rates of breathing during airway constriction by methacholine. The indices have detected the acute airway obstruction even at high frequencies, frequencies usually presented by infants during an acute bronchoconstriction
Silva, Ronaldo Aparecido da. "Estudo dos mecanismos induzidos pelo treinamento físico aeróbico ao longo do tempo na inflamação pulmonar e no remodelamento brônquico em um modelo murino de asma." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-01112013-105844/.
Full textThe aerobic training (AT) promotes benefits for asthmatics, but the anti-inflammatory mechanisms are not known. Experimental studies of asthma have shown that AT reduces the pulmonary allergic chronic inflammation (PACI) and response Th2, however no study has ever explained when the protective effects are initiated and which is the main anti-inflammatory pathway triggered. Aim: To evaluate the effect of AT over time in a murine model of asthma to identify when the anti-inflammatory effects is started and reverse bronchial remodeling (BR). Methods: BALB/c (160 mice) were divided into 4 groups: Control (CT): not induced to PACI and untrained; Aerobic Training (TA): not induced to PACI and trained; OVA: induced to PACI and untrained; OVA + TA: induced to PACI and trained. After that were created others subgroups 1, 3, 7, 15 and 30 days AT, that is, each group was repeated 5 times to investigate the effect of AT over time. The OVA groups were sensitized with i.p. OVA (OVA+AlumHidrox), and then the mice were induced after the PACI with aerosol of OVA (1-3%) started on the 21st day (3 x week, 30 min./Session). Adaptation to TA was held between 21-23, on the 25th day the physical test was performed, and on day 28 AT was begun (50% intensity, frequency x 5 for 4 weeks). Twenty four hours of the after last session of AT (1, 3, 7, 15 and 30 days) the mice were anesthetized, euthanized and the bronchoalveolar lavage fluid was collected (BALF) (Total and differential cell count) and blood was used to quantify immunoglobulins (IgE and IgG1) by passive cutaneous anaphylaxis reaction (PCA) technique, the pulmonary tissue was removed and used to evaluate the mediators IL-4, IL-5, eotaxin, RANTES, ICAM-1, VCAM-1, TGF-b, VEGF, osteopontin (OPN), NF-kB, FOXP3, glucocorticoid receptor (GR), and antiinflammatory IL-10 and IL-1ra (immunohistochemistry and quantified by morphometry), was also the quadriceps muscle to assess the expression of myokines (IL-10, IL-1ra and IL-6) (by immunohistochemistry and image analyses). The BR (smooth muscle, epithelium, collagen and elastic fibers deposition, and mucus production) was also evaluated by image analysis. Results: It was not observed any production of myokines (p>0.05). The levels of IgE and IgG1, cell migration, production of inflammatory mediators, and the BR were increased in the OVA groups (p<0.05); that still showed a decreased production of the GR (p<0.05). The AT promoted an increase of GR in the airway smooth muscle from the 3rd day, the production of IL-10 and IL- 1ra were increased from day 7 for cells peribronchial, while NF-kB, IL-4, IL-5, eotaxin, RANTES, ICAM-1, VCAM-1, VEGF, eosinophil counting in BALF were reduced, and reversed the smooth muscle thickening, epithelium and deposition of collagen fibers too (p<0.05). Interestingly, the decreasing of TGF-b occurred in the 3rd day, and OPN, elastic fibers, mucus occurred after 15 days of AT, while IgE and IgG1, and neutrophils were reduced only after 30 days (p<0.05). Conclusion: The anti-inflammatory mechanism by increasing the GR on the smooth muscle of the airways was initiated from the 3rd day of the AT, followed by an increase of IL-10 and IL-1ra and a reduction of NF-kB from the 7th day of the AT, reversed the effects of chronic allergic inflammation and bronchial remodeling
Everaere, Laëtitia. "Rôle des cellules lymphoïdes dans l’exacerbation de l’asthme par des co-facteurs environnementaux." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S001.
Full textThe prevalence of asthma has increased twice in Western countries since about 1980. An alarming growth which correlates with lifestyle changes: sanitary conditions (exposure to infectious agents), nutrition, or pollution. These elements are risk co-factors, involved in asthma development or aggravation. However, no clear mechanism is determined to date. This work focused on the role of central players in the immune response, the innate and adaptive lymphoid populations in asthma exacerbation by these different cofactors.Obesity is associated with an increased prevalence of asthma. Recently, the innate lymphoid cells (ILC) were involved in these 2 pathologies. The main focus of my work was to characterize the T cells compared to ILC contribution in a murine model of asthma exacerbation induced by mite allergens linked to obesity. A high fat diet leads to the exacerbation of the main asthma features, including bronchial hyperresponsiveness, humoral response, recruitment of circulating and tissue eosinophils. In parallel to the exacerbation of Th2 and Th17 profiles, the amount of activated ILC2 and ILC3 is amplified in the lung of obese asthmatic mice and associated with increased expression of IL-33, IL-1β and reduced ILC markers in visceral adipose tissue. ILC depletion in this model confirmed their involvement in asthma exacerbation in obese mice, especially through Th2 and Th17 profiles activation.On the other hand, we evaluated the impact of PAH, pollutants from diesel exhaust, by monitoring the molecular characteristics of severe asthma. Among the activated blood mononuclear cells, diesel exhaust particles (DEP)-PAH and those of benzo[a]pyrene (B[a]P) enhance IL-22 production in asthmatic allergic patients (AA), and decrease IL-17A. Th22 cells are the major source of this IL-22 production and its induction mechanism is mainly dependent on AhR under the effect of DEP-PAH contrary to B[a]P.Finally, we investigated the impact of infections. NOD1 priming of human dendritic cells (DC), independently of the allergen presentation, promoted a Th2 polarization profile which involved the production of both CCL17 and CCL22 in nonallergic subjects but only CCL17 in allergic patients. Moreover, NOD1-primed DC from allergic donors exhibited enhanced maturation that led to abnormal CCL22 and IL-10. In mice, systemic NOD1 activation exacerbates allergic asthma, via the increase in pulmonary Th2 response depending on CCL17.In another study, the costimulation of human immature DC, by dog allergen and TLR3 or TLR9 ligands, increases the DC differentiation, expression of activation markers and cytokine production, with the induction of a Th22/Th1 profile in healthy subjects, unlike a Th22/Th17/Th2 profile in AA patients. This specific DC activation, induced by costimulation in AA patients, leads to the IL-17A, IL-17F and IL-13 secretion, as well as the amplification of IL-22 production by Th22 cells. All this suggests that costimulation by certain allergens and/or pathogens can induce Th22 and Th17 response in asthmatic subjects, and may contribute to the severity of some asthma cases.Taken together, the results presented in this work establish new apprehensions of potential asthma determinants, as well as new concepts of molecular and cellular mechanisms underlying the immune response
Irusen, Elvis Malcolm. "Glucocorticosteroid receptor characteristics of peripheral blood mononuclear cells in oral steroid dependent asthma : utilization of an in vitro model of steroid resistant asthma to investigate mechanisms of resistance and functional consequences of altered receptor affinity." Thesis, 2007. http://hdl.handle.net/10413/2527.
Full textThesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2007.
Saurek-Aleksandrovska, Natalija. "Association between insulin resistance, metabolic syndrome, asthma and the other asthma phenotypes." 2013. http://hdl.handle.net/1993/21618.
Full textHerbert, Cristan Medical Sciences Faculty of Medicine UNSW. "Effects of glucocorticoid and phosphodiesterase-4 inhibitor therapy in a mouse model of chronic asthma." 2007. http://handle.unsw.edu.au/1959.4/40535.
Full textKlaßen, Carina. "Airway Epithelial Cells as Targets of Glucocorticoid Therapy in Inflammatory Lung Diseases." Doctoral thesis, 2017. http://hdl.handle.net/11858/00-1735-0000-0023-3DB4-1.
Full textWilliams, Deon. "Effects of -tocopherol supplementation on dexamethasone-induced insulin resistance." Master's thesis, 2010. http://hdl.handle.net/10048/1372.
Full textNutrition and Metabolism
Pinkerton, James. "Elucidating the mechanisms of steroid-resistant asthma." Thesis, 2018. http://hdl.handle.net/1959.13/1383707.
Full textSevere, steroid-resistant (SSR) asthma is of considerable clinical and economic significance as affected individuals do not respond to mainstay corticosteroid therapies. Patients with SSR asthma experience more frequent exacerbations of disease, are more likely to require hospitalisation and have a poor quality of life. Improved therapies are urgently required for SSR asthma, however, progress in this area has been hampered by a lack of understanding of the pathological processes that underpin disease. The major obstacle to understanding the processes that drive SSR asthma is that there are several subsets of the disease characterised by different inflammatory and immunological phenotypes. This heterogeneity disease makes pinpointing the key processes that underpin disease extremely difficult in humans. To help understand the mechanisms that underpin SSR asthma, we have developed three unique infection-induced models of SSR asthma. As part of my thesis, I have also developed a high fat diet-induced, obesity-associated SSR asthma. Together, all four models recapitulate the key features of a number of different subsets/clusters of SSR asthma in the clinic and represent useful tools to understand subset-specific and universal factors/processes that underpin of disease and test novel therapies that target the factors/processes identified. The overarching aim of my PhD is to utilise these models to elucidate novel mechanisms that may underpin SSR asthma and to determine whether targeting these mechanisms with therapeutic interventions can suppress disease, where steroids are not effective. My PhD was divided into three major aims that have focused on discovering novel factors associated with disease and assessing the roles played by known associative factors potentially drive steroid resistance. Firstly, I conducted array analyses on whole lung tissue from our three models of infection-induced SSR asthma, that represent different inflammatory and immune subsets observed in the clinic, to identify factors that are universally dysregulated in disease. I identified 11 universally dysregulated genes, most of which have not been previously recognised in SSR asthma (chapter 2). I then showed the functional role that one of these factors may being playing in driving SSR asthma (chapter 2). Secondly, I have identified dysregulated antioxidant responses as playing a critical role in our Chlamydia-induced model of SSR asthma and show that restoration of antioxidant responses may be a beneficial adjunct therapy for steroid-resistant disease (chapter 3). Lastly, I have developed a new murine model of high fat diet (HFD)-induced obesity that induces SSR allergic airways disease (AAD) (chapter 4). I used this model to identify a previously unrecognised role for HFD/obesity-induced, NLRP3 inflammasome-mediated responses in the lung the development of steroid-resistant airways hyper-responsiveness (AHR). I also show that HFD/obesity induced NLRP3 inflammasome responses in the lung may be therapeutically targeted for the treatment of HFD/obesity-associated, steroid-resistant AHR. Together the findings from my PhD studies inform new mechanisms and pathways that may underpin SSR asthma in the clinical setting and highlight potential therapeutic targets and strategies for the treatment of disease. The development of a representative obesity-induced model of SSR asthma will be a useful tool for future studies that aim to identify mechanisms and treatment strategies for obese SSR asthmatics.
Li, Jingjing. "Respiratory innate immune factors regulate steroid-resistant airway hyperreactivity and asthma." Thesis, 2014. http://hdl.handle.net/1959.13/1045322.
Full textAsthma is a chronic inflammatory disease of the airways and a combination of genetic and environmental factors underpin the pathogenesis. The clinical symptoms of asthmatics most mild to moderate, allergic asthma patients can be effectively managed by combination therapy with broad-spectrum anti-inflammatory agents and bronchodilators (typically inhaled glucocorticoids and long acting β-agonists). Indeed, glucocorticoids remain the forefront therapeutical approaches for the treatment of asthma. However, 5-10% of asthmatics who have severe asthma do not respond to treatment, and these patients account for almost 50% of asthma-related healthcare costs. Thus it is essential to understand the pathogenesis of steroid resistance in severe asthma for the development of more efficient therapies for those patients. With well-established animal models of steroid resistant airway hyper-responsiveness (AHR, a hallmark feature of asthma) and in vitro culture systems of pulmonary macrophages, the underlying mechanisms regulating steroid resistance and exacerbation of asthma have been thoroughly investigated, particularly on the causative roles of innate immune factors. This thesis consists of three publications. The first publication identifies changes in the expression of key innate immune molecules and their signalling pathways in a mouse model of steroid-resistant AHR and demonstrates the central role of pulmonary macrophages in the induction of steroid-resistant AHR The second publication investigates the expression of olfactory receptors in the respiratory system and on immune cells in response to innate immune activation, and identifies a potential role of olfactory receptors in regulating the function of pulmonary macrophages. The final publication discusses the modulation of small non-coding RNAs, microRNA, expression by innate immune activation in a steroid-resistant mouse model of asthma and evaluates the role of key microRNAs involved in the induction of steroid-resistant AHR by regulating the activity of a critical phosphatase, protein phosphatase-2A, which further affected the function of glucocorticoid.
Hennig, Heike. "Untersuchungen zu molekularen Mechanismen der Glucocorticoid-Resistenz bei Akuter Lymphatischer Leukämie (ALL)." Doctoral thesis, 2003. http://hdl.handle.net/11858/00-1735-0000-0006-AD8E-E.
Full textHadjigol, Sara. "Understanding the mechanisms of bacterial-induced exacerbation of allergic airways disease in a mouse model." Thesis, 2017. http://hdl.handle.net/1959.13/1349583.
Full textActivation of innate immune responses in individuals with asthma by respiratory viral and bacterial infections or colonization with pathogenic bacteria can cause disease exacerbation. Exacerbations have a negative impact on quality of life and are characterised by persistent airway inflammation, worsening of disease symptoms and poor responsiveness to standard corticosteroid therapy. How activation of innate host defence pathways by bacterial infection triggers steroid-resistant inflammatory pathways and disease exacerbation is poorly understood. Better disease models are urgently required to identify mechanisms underlying disease exacerbation. We hypothesised that bacterial infection (mimicked by lipopolysaccharide (LPS) exposure) would exacerbate pre-existing allergic airways disease (AAD) in a mouse model, causing steroid-resistant airways inflammation and airway hyperresponsiveness (AHR). Mice were initially sensitized and subsequently challenged with nebulised ovalbumin (OVA) to induce AAD. LPS was then administered into the lung, in the presence or absence of dexamethasone (DEX) to assess steroid sensitivity. Disease outcomes were assessed by quantifying lung function (airways hyperresponsiveness; AHR), inflammatory cell infiltration, tissue cytokine levels and microarray profiling. LPS administration induced steroid-resistant AHR and increased inflammatory cytokine expression (including interleukin (IL)-27, interferon (IFN)γ, macrophage inflammatory protein (MIP)-1α and tumour necrosis factor α (TNFα)), while CD4+ T-helper 2 (Th2) cytokines (IL-5 and IL-13) were not altered compared to OVA-treated mice. Neutrophil and macrophage numbers were also increased in the bronchoalveolar fluid (BALF) following LPS administration. Targeted depletion of alveolar macrophages with 2-chloroadenosine (2-CA) significantly suppressed AHR. Further, IL-13 was required for exacerbation, as LPS failed to exacerbate AHR in IL-13 deficient mice or following administration of IL-13 blocking antibodies. Microarray profiling of lung samples revealed that microRNA (miR)-135b-5p expression was markedly increased following LPS administration in mice with pre-existing AAD and expression was only partially suppressed by corticosteroid treatment. Inhibition of miR-135b-5p function by antagomir treatment suppressed LPS-induced exacerbations AHR and markedly reduced inflammatory cell infiltration. In summary, we developed a novel mouse model of LPS-induced steroid-resistant exacerbation of AAD, which mimic critical features of infection-induced exacerbation of asthma. Our findings highlight key roles for pulmonary macrophages, IL-13 and miR-135b-5p in the development of disease symptoms. Targeting these pathways may be a useful treatment for acute bacterial-induced exacerbation of asthma.
Kim, Richard Yong Hoon. "Investigation of the mechanisms of respiratory infection-induced lung disease." Thesis, 2015. http://hdl.handle.net/1959.13/1060846.
Full textChlamydia respiratory infections have been widely linked with the development and exacerbation of asthma, particularly more severe forms of asthma, in both children and adults. Murine models of Chlamydia respiratory infection and AAD were used to investigate the mechanisms that underpin the association between infection and asthma. We have made important and novel observations that demonstrate how neonatal Chlamydia infection results in chronic lung disease. We show that neonatal Chlamydia infection induces a group of 5 miRNAs (miR-155, miR-21, miR-223, miR-146b and miR-203) during infection and that the therapeutic inhibition of each miRNA can prevent the development of key disease features, including lung inflammation and histopathology, persistent AHR, emphysema-like alveolar enlargement and increased severity of AAD in later life. We have also made important and novel observations that further our understanding of the mechanisms that underpin the association between Chlamydia respiratory infection and severe, steroid-insensitive asthma. We demonstrate that Chlamydia respiratory infection in established AAD induces a miR-21/PI3K/pAkt/HDAC2 signalling axis to promote severe, steroid-insensitive AAD. Importantly, the therapeutic inhibition of Chlamydia-induced miR-21 and/or PI3K signalling restores sensitivity to steroid treatment. Additionally, the therapeutic inhibition of miR-21 also suppresses the key features of Haemophilus respiratory infection-induced, severe, steroid-insensitive AAD. We also demonstrate that Chlamydia respiratory infection induces an NLRP3 inflammasome/Caspase-1/IL-1β signalling axis to promote severe, steroid-insensitive AAD. Importantly, the therapeutic inhibition of Chlamydia-induced NLRP3 inflammasome and/or Caspase-1 and/or IL-1β signalling restores sensitivity to steroid treatment. Furthermore, the therapeutic inhibition of each component of this axis also suppresses the key features of Haemophilus respiratory infection-induced, severe, steroid-insensitive AAD. Our studies significantly contribute to understanding the role of neonatal Chlamydia respiratory infection in the development of chronic lung disease and severe asthma in later life, and the roles of Chlamydia and Haemophilus respiratory infections in promoting severe, steroid-insensitive asthma. Importantly, our studies suggest that therapeutically targeting key Chlamydia and Haemophilus respiratory infection-induced factors in the lung may be effective for the prevention and/or treatment of severe asthma.
Nguyen, Thi Hiep. "Modeling of respiratory syncytial virus-induced exacerbation of allergic airways disease." Thesis, 2017. http://hdl.handle.net/1959.13/1337694.
Full textAsthma is a chronic inflammatory disorder of the airways characterised by clinical symptoms such as wheeze, shortness of breath, airflow obstruction, mucus hypersecretion and airway hyper-responsiveness (AHR). Numerous factors contribute to the pathogenesis of asthma, including respiratory infections, allergens, pollution and smoking. These factors can trigger asthma exacerbations, which are defined as a worsening of clinical symptoms. Asthma exacerbations are a major cause of hospitalisation and occur in all asthmatic patients regardless of disease severity. Although mild-to-moderate asthma can generally be well-controlled with glucocorticoid (GC) treatment, exacerbations are often difficult to treat and new effective approaches are needed. Viral respiratory infections, such as respiratory syncytial virus (RSV), are associated with exacerbations in patients with pre-existing asthma. Although allergic asthma is critically regulated by increased CD4+ T-helper (Th) type 2 (Th2) responses and type 2 innate lymphoid cells (ILC2s), viral infections are thought to exacerbate asthma by enhancing allergic inflammation and/or through activation of innate immune responses. Clinical studies have identified a complex range of immune responses during viral-induced exacerbations involving Th2, Th1 and Th17 responses, and activation of host innate immunity including macrophages. However, the disease mechanisms and the role of innate immune responses in particular, which underlie viral-induced exacerbations remain poorly understood. The aim of this PhD project was to establish a mouse model of RSV-induced exacerbations, which presents hallmark features of viral-induced exacerbations in humans. This model was then used to investigate the immunological mechanisms underpinning disease, and to identify new potential approaches for treatment. Chapter 2 describes the development and characterisation of our RSV-induced exacerbation model of AHR and airway inflammation in a mouse model of pre-existing allergic airways disease (AAD). Exacerbation was associated with activation of innate host immune responses. Notably, exacerbation only occurred on the background of AAD, indicating the importance of an underlying type 2 environment for pathogenesis. Further, RSV-induced exacerbation failed to respond to GC treatment. In this study, key functional roles for tumour necrosis factor-alpha (TNFα), monocyte chemoattractant protein (MCP)-1 and pulmonary macrophages in exacerbation were demonstrated through intervention studies. Further, increased TNFα and MCP-1 expression was observed in neutrophilic asthmatic patients, a subpopulation that often poorly respond to GC treatment. Chapter 3 investigated the role of the pro-inflammatory cytokines interferon-gamma (IFN-γ) and interleukin (IL)-27 as key regulators in the model of RSV-induced steroid-resistant exacerbation. RSV-induced exacerbation increased expression of IFN-γ and IL-27, which was resistant to GC treatment. Neutralisation of either IFN-γ or IL-27 completely suppressed RSV-induced AHR. This study further highlighted the role of these molecules in conjunction with macrophages in the induction of RSV-induced exacerbation. In Chapter 4, the effectiveness of a new anti-inflammatory bromodomain and extra terminal (BET) inhibitor (I-BET) was assessed for the suppression of steroid-resistant AHR. Two steroid-resistant airways disease models; a previously-described short-term model induced by IFN-γ and lipopolysaccharide (LPS) administration to the lung (two factors linked to steroid-resistant asthma) and our RSV-induced exacerbation model (Chapter 2) were used. I-BET treatment effectively suppressed AHR and airway inflammation in both models, by inhibiting the activation of pulmonary macrophages. These findings suggest that inhibition of BET proteins may be a novel therapeutic pathway to treat asthma exacerbations, by targeting macrophages. Thus these investigations indicate that in the context of underlying pre-existing allergic airways inflammation (found in asthma), RSV infection stimulates innate immune responses, increasing inflammation and AHR. In particular, key roles for TNFα, MCP-1, IFN-γ, IL-27 and pulmonary macrophages in the pathogenesis of RSV-induced exacerbation were demonstrated. Further, the new anti-inflammatory reagent, I-BET, was shown to significantly suppress all key features of RSV-induced steroid-resistant exacerbation (e.g inflammation and AHR) and IFN-γ/LPS-induced steroid-resistant AHR. These observations provide evidence for an important role of BET proteins in the regulation of steroid-resistant AHR and airway inflammation. Therefore, these studies provide evidence that targeting innate immune activation could be a therapeutic approach for the treatment of viral-induced asthma exacerbation.