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Elucidation of the Aetiology of Airway Remodelling in COPD

Project Member(s): Oliver, B.

Funding or Partner Organisation: National Health & Medical Research Council (NHMRC Project Grants)

Start year: 2016

Summary: Cigarette smoking causes chronic obstructive pulmonary disease (COPD), in which the majority of the disease burden is caused by small airways remodeling. This is characterised by increased airway wall thickness as a result of excessive extracellular matrix (ECM) deposition, relates to the clinical progression of COPD, is not reversible upon smoking cessation, and is not treated by current therapeutic regimens. In ground-breaking experiments we have discovered that cigarette smoke extract (CSE) induces the release of specific ECM proteins in airway cells from people with COPD, whilst in people without COPD no release occurs. In each airway cell type we have examined the profile of cigarette smoke induced ECM is different. We do not know the reason why the COPD cells have this altered behavior. However we know the signalling pathway by which cigarette smoke induces ECM release in COPD cells, and know this is different to how the profibrotic factor TGF induces ECM. We also think that epigenetic changes are likely to be important as in our preliminary studies we have used the histone deacetylase (HDAC) inhibitor trichostatin A and found it affects ECM mRNA in only COPD fibroblasts, and we have also found that statins, which also inhibit HDACs, can inhibit cigarette smoke-induced ECM. Given these findings our overall aims are to compressively characterize the production of cigarette smoke induced ECM, understand why only COPD cells respond to cigarette smoke (by epigenetic control mechanisms), and to investigate if it is possible to inhibit cigarette smoke induced ECM.

Publications:

Bozier, J, Rutting, S, Xenaki, D, Peters, M, Adcock, I & Oliver, BG 2019, 'Heightened response to e-cigarettes in COPD.', ERJ open research, vol. 5, no. 1.
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Chan, YL, Wang, B, Chen, H, Ho, KF, Cao, J, Hai, G, Jalaludin, B, Herbert, C, Thomas, PS, Saad, S & Oliver, BGG 2019, 'Pulmonary inflammation induced by low-dose particulate matter exposure in mice.', American journal of physiology. Lung cellular and molecular physiology, vol. 317, no. 3, pp. L424-L430.
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Li, G, Chan, YL, Nguyen, LT, Mak, C, Zaky, A, Anwer, AG, Shi, Y, Nguyen, T, Pollock, CA, Oliver, BG, Saad, S & Chen, H 2019, 'Impact of maternal e-cigarette vapor exposure on renal health in the offspring', ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, vol. 1452, no. 1, pp. 65-77.
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McAlinden, KD, Deshpande, DA, Ghavami, S, Xenaki, D, Sohal, SS, Oliver, BG, Haghi, M & Sharma, P 2019, 'Autophagy Activation in Asthma Airways Remodeling.', American Journal of Respiratory Cell and Molecular Biology, vol. 60, no. 5.
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Li, G, Saad, S, Oliver, BG & Chen, H 2018, 'Heat or Burn? Impacts of Intrauterine Tobacco Smoke and E-Cigarette Vapor Exposure on the Offspring's Health Outcome.', Toxics, vol. 6, no. 3.
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Nissen, G, Hollaender, H, Tang, FSM, Wegmann, M, Lunding, L, Vock, C, Bachmann, A, Lemmel, S, Bartels, R, Oliver, BG, Burgess, JK, Becker, T, Kopp, MV & Weckmann, M 2018, 'Tumstatin fragment selectively inhibits neutrophil infiltration in experimental asthma exacerbation', CLINICAL AND EXPERIMENTAL ALLERGY, vol. 48, no. 11, pp. 1483-1493.
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Tonga, KO, King, GG, Farah, CS, Thamrin, C, Tang, FS, Santos, J, Sharma, P, Chapman, DG & Oliver, BG 2018, 'Steroid insensitive fixed airflow obstruction is not related to airway inflammation in older non-smokers with asthma.', Respiratory research, vol. 19, no. 1, pp. 176-176.
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Rutting, S, Horvat, J, Wood, L, Hansbro, P & Oliver, B 2018, 'The effect of dietary fatty acids on respiratory infection in human lung cells', EUROPEAN RESPIRATORY JOURNAL, International Congress of the European-Respiratory-Society, EUROPEAN RESPIRATORY SOC JOURNALS LTD, Paris, France.
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Zakarya, R, Chen, H, Brandsma, CA, Adcock, IM & Oliver, BG 2018, 'Role of Histone Acetylation in Fibrosis in Chronic Obstructive Pulmonary Disease', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, International Conference of the American-Thoracic-Society, AMER THORACIC SOC, San Diego, CA.

Kota, A, Deshpande, D, Haghi, M, Oliver, B & Sharma, P 2017, 'Autophagy and airway fibrosis: Is there a link?', F1000 Research, vol. 6, no. 409, pp. 1-10.
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Sharma, P, Yi, R, Nayak, A, Wang, N, Knight, MJ, Pan, S, Oliver, B & Deshpande, DA 2017, 'Bitter Taste Receptor Agonists Mitigate Features of Allergic Asthma in Mice.', Scientific Reports, vol. 7, pp. 1-14.
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Turturice, BA, McGee, HS, Oliver, B, Baraket, M, Nguyen, BT, Ascoli, C, Ranjan, R, Rani, A, Perkins, DL & Finn, PW 2017, 'Atopic asthmatic immune phenotypes associated with airway microbiota and airway obstruction.', PLoS ONE, vol. 12, no. 10, pp. 1-18.
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Capistrano, SJ, Zakarya, R, Chen, H & Oliver, BG 2016, 'Biomass Smoke Exposure Enhances Rhinovirus-Induced Inflammation in Primary Lung Fibroblasts', INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 17, no. 9.
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Tang, FS, Hansbro, PM, Burgess, JK, Ammit, AJ, Baines, KJ & Oliver, BG 2016, 'A novel immunomodulatory function of neutrophils on rhinovirus-activated monocytes in vitro.', Thorax, vol. 71, no. 11, pp. 1039-1049.
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FOR Codes: Respiratory System and Diseases (incl. Asthma), Respiratory Diseases