BibTex format
@article{Ali:2020:10.1183/13993003.01340-2019,
author = {Ali, MK and Kim, RY and Brown, AC and Mayall, JR and Karim, R and Pinkerton, JW and Liu, G and Martin, KL and Starkey, MR and Pillar, A and Donovan, C and Pathinayake, PS and Carroll, OR and Trinder, D and Tay, HL and Badi, YE and Kermani, NZ and Guo, Y-K and Aryal, R and Mumby, S and Pavlidis, S and Adcock, IM and Weaver, J and Xenaki, D and Oliver, BG and Holliday, EG and Foster, PS and Wark, PA and Johnstone, DM and Milward, EA and Hansbro, PM and Horvat, JC},
doi = {10.1183/13993003.01340-2019},
journal = {European Respiratory Journal},
pages = {1--14},
title = {Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma.},
url = {http://dx.doi.org/10.1183/13993003.01340-2019},
volume = {55},
year = {2020}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Accumulating evidence highlights links between iron regulation and respiratory disease. Here, we assessed the relationship between iron levels and regulatory responses in clinical and experimental asthma.We show that cell-free iron levels are reduced in the bronchoalveolar lavage (BAL) supernatant of severe or mild-moderate asthma patients and correlate with lower forced expiratory volume in 1s (FEV1). Conversely, iron-loaded cell numbers were increased in BAL in these patients and with lower FEV1/forced vital capacity (FEV1/FVC). The airway tissue expression of the iron sequestration molecules divalent metal transporter 1 (DMT1) and transferrin receptor 1 (TFR1) are increased in asthma with TFR1 expression correlating with reduced lung function and increased type 2 (T2) inflammatory responses in the airways. Furthermore, pulmonary iron levels are increased in a house dust mite (HDM)-induced model of experimental asthma in association with augmented Tfr1 expression in airway tissue, similar to human disease. We show that macrophages are the predominant source of increased Tfr1 and Tfr1+ macrophages have increased Il13 expression. We also show that increased iron levels induce increased pro-inflammatory cytokine and/or extracellular matrix (ECM) responses in human airway smooth muscle (ASM) cells and fibroblasts ex vivo and induce key features of asthma, including airway hyper-responsiveness and fibrosis and T2 inflammatory responses, in vivoTogether these complementary clinical and experimental data highlight the importance of altered pulmonary iron levels and regulation in asthma, and the need for a greater focus on the role and potential therapeutic targeting of iron in the pathogenesis and severity of disease.
AU - Ali,MK
AU - Kim,RY
AU - Brown,AC
AU - Mayall,JR
AU - Karim,R
AU - Pinkerton,JW
AU - Liu,G
AU - Martin,KL
AU - Starkey,MR
AU - Pillar,A
AU - Donovan,C
AU - Pathinayake,PS
AU - Carroll,OR
AU - Trinder,D
AU - Tay,HL
AU - Badi,YE
AU - Kermani,NZ
AU - Guo,Y-K
AU - Aryal,R
AU - Mumby,S
AU - Pavlidis,S
AU - Adcock,IM
AU - Weaver,J
AU - Xenaki,D
AU - Oliver,BG
AU - Holliday,EG
AU - Foster,PS
AU - Wark,PA
AU - Johnstone,DM
AU - Milward,EA
AU - Hansbro,PM
AU - Horvat,JC
DO - 10.1183/13993003.01340-2019
EP - 14
PY - 2020///
SN - 0903-1936
SP - 1
TI - Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma.
T2 - European Respiratory Journal
UR - http://dx.doi.org/10.1183/13993003.01340-2019
UR - https://www.ncbi.nlm.nih.gov/pubmed/32184317
UR - https://erj.ersjournals.com/content/early/2020/01/24/13993003.01340-2019.article-info
UR - http://hdl.handle.net/10044/1/77654
VL - 55
ER -
