Imperial College London

ProfessorRosemaryBoyton

Faculty of MedicineDepartment of Infectious Disease

Professor of Immunology and Respiratory Medicine
 
 
 
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Contact

 

r.boyton

 
 
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Location

 

8N22Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Reynolds:2018:10.1165/rcmb.2018-0007OC,
author = {Reynolds, CJ and Quigley, K and Cheng, X and Suresh, A and Tahir, S and Ahmed-Jushuf, F and Nawab, K and Choy, K and Walker, SA and Mathie, SA and Sim, M and Stowell, J and Manji, J and Pollard, T and Altmann, DM and Boyton, RJ},
doi = {10.1165/rcmb.2018-0007OC},
journal = {American Journal of Respiratory Cell and Molecular Biology},
pages = {557--571},
title = {Lung defense through interleukin-8 carries a cost of chronic lung remodeling and impaired function},
url = {http://dx.doi.org/10.1165/rcmb.2018-0007OC},
volume = {59},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - RATIONALE: IL-8 dependent inflammation is a hallmark of host lung innate immunity to bacterial pathogens, yet in many human lung diseases including COPD, bronchiectasis, and pulmonary fibrosis, there are progressive, irreversible pathologic, changes associated with elevated levels of IL-8 in the lung. OBJECTIVES: To better understand the duality of IL-8 dependent host immunity to bacterial infection and lung pathology, we targeted human IL-8 to express transgenically in murine bronchial epithelium, investigating the impact of over-expression on lung bacterial clearance, host immunity, lung pathology and function. MEASUREMENTS AND MAIN RESULTS: Persistent IL-8 expression in bronchial epithelium resulted in neutrophilia, neutrophil maturation, activation and chemtoaxis. There was enhanced protection from challenge with Pseudomonas aeruginosa and significant changes in baseline expression of innate and adaptive immunity transcripts for Ccl5, Tlr6, IL2 and Tlr1. There was increased expression of Tbet and Foxp3 in response to the Pseudomonas antigen, OprF, indicating a regulatory T cell phenotype. However, this enhanced bacterial immunity comes at the high price of progressive lung remodelling, with increased inflammation, mucus hyper-secretion, and fibrosis. There is increased expression of Ccl3 and reduced expressioh of Claudin 18 and F11r, with damage to epithelial organization leading to leaky tight junctions, all resulting in impaired lung function with reduced compliance, increased resistance and bronchial hyperreactivity measured by whole body plethysmography. CONCLUSIONS: IL-8 over-expression in the bronchial epithelium benefits lung immunity to bacterial infection, but specifically drives lung damage through persistent inflammation, lung remodelling and damaged tight junctions, leading to impaired lung function.
AU - Reynolds,CJ
AU - Quigley,K
AU - Cheng,X
AU - Suresh,A
AU - Tahir,S
AU - Ahmed-Jushuf,F
AU - Nawab,K
AU - Choy,K
AU - Walker,SA
AU - Mathie,SA
AU - Sim,M
AU - Stowell,J
AU - Manji,J
AU - Pollard,T
AU - Altmann,DM
AU - Boyton,RJ
DO - 10.1165/rcmb.2018-0007OC
EP - 571
PY - 2018///
SN - 1044-1549
SP - 557
TI - Lung defense through interleukin-8 carries a cost of chronic lung remodeling and impaired function
T2 - American Journal of Respiratory Cell and Molecular Biology
UR - http://dx.doi.org/10.1165/rcmb.2018-0007OC
UR - https://www.ncbi.nlm.nih.gov/pubmed/29894204
UR - http://hdl.handle.net/10044/1/60795
VL - 59
ER -