Imperial College London

DrJamesPinkerton

Faculty of MedicineNational Heart & Lung Institute

Research Associate
 
 
 
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Contact

 

j.pinkerton

 
 
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Location

 

G67Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

12 results found

Ali MK, Kim RY, Brown AC, Donovan C, Vanka KS, Mayall JR, Liu G, Pillar AL, Jones-Freeman B, Xenaki D, Borghuis T, Karim R, Pinkerton JW, Aryal R, Heidari M, Martin KL, Burgess JK, Oliver BG, Trinder D, Johnstone DM, Milward EA, Hansbro PM, Horvat JCet al., 2020, Critical role for iron accumulation in the pathogenesis of fibrotic lung disease, JOURNAL OF PATHOLOGY, Vol: 251, Pages: 49-62, ISSN: 0022-3417

Journal article

Pinkerton J, Kim R, Brown A, Rae B, Mayall J, Ali MK, Starkey M, Robertson A, Wood L, Cooper M, O’Neill L, Hansbro P, Horvat Jet al., 2019, IL-5/IL-13 drive NLRP3 inflammasome-mediated, steroid-resistant AHR in a model of obesity-associated asthma, ERS International Congress 2019 abstracts, Publisher: European Respiratory Society

Conference paper

Pinkerton J, Kim R, Robertson A, Hirota J, Wood L, Knight D, Cooper M, O'Neill L, Horvat J, Hansbro Pet al., 2017, Inflammasomes in the lung, Molecular Immunology, ISSN: 0161-5890

Journal article

Kim RY, Pinkerton JW, Essilfie AT, Robertson AAB, Baines KJ, Brown AC, Mayall JR, Ali MK, Starkey MR, Hansbro NG, Hirota JA, Wood LG, Simpson JL, Knight DA, Wark PA, Gibson PG, O'Neill LAJ, Cooper MA, Horvat JC, Hansbro PMet al., 2017, Role for NLRP3 Inflammasome-mediated, IL-1 beta-Dependent Responses in Severe, Steroid-Resistant Asthma, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 196, Pages: 283-297, ISSN: 1073-449X

Journal article

Horvat J, Kim R, Pinkerton J, Essilfie A-T, Robertson A, Baines K, Mayall J, Starkey M, Wark P, Gibson P, O'Neill L, Cooper M, Hansbro Pet al., 2016, NLRP3 inflammasome-mediated, IL-1 beta-dependent inflammatory responses drive steroid-resistant asthma, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Pinkerton J, Kim R, Essilfie A-T, Rae B, Mayall J, Ali MK, Starkey M, Wood L, Biswal S, Horvat J, Hansbro Pet al., 2016, Investigating antioxidant therapy for steroid-resistant asthma, ERS International Congress 2016 abstracts, Publisher: European Respiratory Society

Conference paper

Kim RY, Rae B, Neal R, Donovan C, Pinkerton J, Balachandran L, Starkey MR, Knight DA, Horvat JC, Hansbro PMet al., 2016, Elucidating novel disease mechanisms in severe asthma, Clinical & Translational Immunology, Vol: 5, Pages: e91-e91

Journal article

Kim RY, Horvat JC, Pinkerton JW, Starkey MR, Essilfie AT, Mayall JR, Nair PM, Hansbro NG, Jones B, Haw TJ, Sunkara KP, Nguyen TH, Jarnicki AG, Keely S, Mattes J, Adcock IM, Foster PS, Hansbro PMet al., 2016, MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase–mediated suppression of histone deacetylase 2, Journal of Allergy and Clinical Immunology, Vol: 139, Pages: 519-532, ISSN: 1097-6825

BACKGROUND: Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease. OBJECTIVE: We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches. METHODS: Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. RESULTS: Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21-specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. CONCLUSION: We identify a previously unrecognized role for an miR-21/PI3K/HDAC2 axis in SSIAAD. Our data

Journal article

Kim RY, Pinkerton JW, Gibson PG, Cooper MA, Horvat JC, Hansbro PMet al., 2015, Inflammasomes in COPD and neutrophilic asthma, Thorax, Vol: 70, Pages: 1199-1201, ISSN: 0040-6376

Journal article

Singanayagam A, Glanville N, Walton RP, Aniscenko J, Pearson RM, Pinkerton JW, Horvat JC, Hansbro PM, Bartlett NW, Johnston SLet al., 2015, A short-term mouse model that reproduces the immunopathological features of rhinovirus-induced exacerbation of COPD, Clinical Science, Vol: 129, Pages: 245-258, ISSN: 1470-8736

Viral exacerbations of chronic obstructive pulmonary disease (COPD), commonly caused by rhinovirus (RV) infections, are poorly controlled by current therapies. This is due to a lack of understanding of the underlying immunopathological mechanisms. Human studies have identified a number of key immune responses that are associated with RV-induced exacerbations including neutrophilic inflammation, expression of inflammatory cytokines and deficiencies in innate anti-viral interferon. Animal models of COPD exacerbation are required to determine the contribution of these responses to disease pathogenesis. We aimed to develop a short-term mouse model that reproduced the hallmark features of RV-induced exacerbation of COPD. Evaluation of complex protocols involving multiple dose elastase and lipopolysaccharide (LPS) administration combined with RV1B infection showed suppression rather than enhancement of inflammatory parameters compared with control mice infected with RV1B alone. Therefore, these approaches did not accurately model the enhanced inflammation associated with RV infection in patients with COPD compared with healthy subjects. In contrast, a single elastase treatment followed by RV infection led to heightened airway neutrophilic and lymphocytic inflammation, increased expression of tumour necrosis factor (TNF)-α, C-X-C motif chemokine 10 (CXCL10)/IP-10 (interferon γ-induced protein 10) and CCL5 [chemokine (C-C motif) ligand 5]/RANTES (regulated on activation, normal T-cell expressed and secreted), mucus hypersecretion and preliminary evidence for increased airway hyper-responsiveness compared with mice treated with elastase or RV infection alone. In summary, we have developed a new mouse model of RV-induced COPD exacerbation that mimics many of the inflammatory features of human disease. This model, in conjunction with human models of disease, will provide an essential tool for studying disease mechanisms and allow testing of novel therapies with pot

Journal article

Essilfie A-T, Horvat JC, Kim RY, Mayall JR, Pinkerton JW, Beckett EL, Starkey MR, Simpson JL, Foster PS, Gibson PG, Hansbro PMet al., 2015, Macrolide therapy suppresses key features of experimental steroid-sensitive and steroid-insensitive asthma, Thorax, Vol: 70, Pages: 458-467, ISSN: 0040-6376

Journal article

Hansbro PM, Kim RY, Pinkerton JW, Starkey MR, Essilfie AT, Mayall JR, Jones B, Haw TJ, Keely S, Mattes J, Adcock IM, Foster PS, Horvat JCet al., 2015, Infection-Induced Microrna-21 Drives Severe, Steroid-Insensitive Experimental Asthma By Amplifying PhosphoINOSitide-3-Kinase (pi3k)-Mediated Suppression Of Histone Deacetylase (hdac)2, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

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