Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation: A Mechanism in Chronic Lung Allograft Dysfunction

Research output: Contribution to journalArticlepeer-review

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Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation : A Mechanism in Chronic Lung Allograft Dysfunction. / Borthwick, L A; Suwara, M I; Carnell, S C; Green, N J; Mahida, R; Dixon, D; Gillespie, C S; Cartwright, T N; Horabin, J; Walker, A; Olin, E; Rangar, M; Gardner, A; Mann, J; Corris, P A; Mann, D A; Fisher, A J.

In: American Journal of Transplantation, Vol. 16, No. 6, 06.2016, p. 1751-65.

Research output: Contribution to journalArticlepeer-review

Harvard

Borthwick, LA, Suwara, MI, Carnell, SC, Green, NJ, Mahida, R, Dixon, D, Gillespie, CS, Cartwright, TN, Horabin, J, Walker, A, Olin, E, Rangar, M, Gardner, A, Mann, J, Corris, PA, Mann, DA & Fisher, AJ 2016, 'Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation: A Mechanism in Chronic Lung Allograft Dysfunction', American Journal of Transplantation, vol. 16, no. 6, pp. 1751-65. https://doi.org/10.1111/ajt.13690

APA

Borthwick, L. A., Suwara, M. I., Carnell, S. C., Green, N. J., Mahida, R., Dixon, D., Gillespie, C. S., Cartwright, T. N., Horabin, J., Walker, A., Olin, E., Rangar, M., Gardner, A., Mann, J., Corris, P. A., Mann, D. A., & Fisher, A. J. (2016). Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation: A Mechanism in Chronic Lung Allograft Dysfunction. American Journal of Transplantation, 16(6), 1751-65. https://doi.org/10.1111/ajt.13690

Vancouver

Author

Borthwick, L A ; Suwara, M I ; Carnell, S C ; Green, N J ; Mahida, R ; Dixon, D ; Gillespie, C S ; Cartwright, T N ; Horabin, J ; Walker, A ; Olin, E ; Rangar, M ; Gardner, A ; Mann, J ; Corris, P A ; Mann, D A ; Fisher, A J. / Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation : A Mechanism in Chronic Lung Allograft Dysfunction. In: American Journal of Transplantation. 2016 ; Vol. 16, No. 6. pp. 1751-65.

Bibtex

@article{4943d4d3f8f8484082c626045875b3d7,
title = "Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation: A Mechanism in Chronic Lung Allograft Dysfunction",
abstract = "Bacterial infections after lung transplantation cause airway epithelial injury and are associated with an increased risk of developing bronchiolitis obliterans syndrome. The damaged epithelium is a source of alarmins that activate the innate immune system, yet their ability to activate fibroblasts in the development of bronchiolitis obliterans syndrome has not been evaluated. Two epithelial alarmins were measured longitudinally in bronchoalveolar lavages from lung transplant recipients who developed bronchiolitis obliterans syndrome and were compared to stable controls. In addition, conditioned media from human airway epithelial cells infected with Pseudomonas aeruginosa was applied to lung fibroblasts and inflammatory responses were determined. Interleukin-1 alpha (IL-1α) was increased in bronchoalveolar lavage of lung transplant recipients growing P. aeruginosa (11.5 [5.4-21.8] vs. 2.8 [0.9-9.4] pg/mL, p < 0.01) and was significantly elevated within 3 months of developing bronchiolitis obliterans syndrome (8.3 [1.4-25.1] vs. 3.6 [0.6-17.1] pg/mL, p < 0.01), whereas high mobility group protein B1 remained unchanged. IL-1α positively correlated with elevated bronchoalveolar lavage IL-8 levels (r(2) = 0.6095, p < 0.0001) and neutrophil percentage (r(2) = 0.25, p = 0.01). Conditioned media from P. aeruginosa infected epithelial cells induced a potent pro-inflammatory phenotype in fibroblasts via an IL-1α/IL-1R-dependent signaling pathway. In conclusion, we propose that IL-1α may be a novel therapeutic target to limit Pseudomonas associated allograft injury after lung transplantation.",
author = "Borthwick, {L A} and Suwara, {M I} and Carnell, {S C} and Green, {N J} and R Mahida and D Dixon and Gillespie, {C S} and Cartwright, {T N} and J Horabin and A Walker and E Olin and M Rangar and A Gardner and J Mann and Corris, {P A} and Mann, {D A} and Fisher, {A J}",
note = "{\textcopyright} Copyright 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.",
year = "2016",
month = jun,
doi = "10.1111/ajt.13690",
language = "English",
volume = "16",
pages = "1751--65",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley",
number = "6",

}

RIS

TY - JOUR

T1 - Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation

T2 - A Mechanism in Chronic Lung Allograft Dysfunction

AU - Borthwick, L A

AU - Suwara, M I

AU - Carnell, S C

AU - Green, N J

AU - Mahida, R

AU - Dixon, D

AU - Gillespie, C S

AU - Cartwright, T N

AU - Horabin, J

AU - Walker, A

AU - Olin, E

AU - Rangar, M

AU - Gardner, A

AU - Mann, J

AU - Corris, P A

AU - Mann, D A

AU - Fisher, A J

N1 - © Copyright 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

PY - 2016/6

Y1 - 2016/6

N2 - Bacterial infections after lung transplantation cause airway epithelial injury and are associated with an increased risk of developing bronchiolitis obliterans syndrome. The damaged epithelium is a source of alarmins that activate the innate immune system, yet their ability to activate fibroblasts in the development of bronchiolitis obliterans syndrome has not been evaluated. Two epithelial alarmins were measured longitudinally in bronchoalveolar lavages from lung transplant recipients who developed bronchiolitis obliterans syndrome and were compared to stable controls. In addition, conditioned media from human airway epithelial cells infected with Pseudomonas aeruginosa was applied to lung fibroblasts and inflammatory responses were determined. Interleukin-1 alpha (IL-1α) was increased in bronchoalveolar lavage of lung transplant recipients growing P. aeruginosa (11.5 [5.4-21.8] vs. 2.8 [0.9-9.4] pg/mL, p < 0.01) and was significantly elevated within 3 months of developing bronchiolitis obliterans syndrome (8.3 [1.4-25.1] vs. 3.6 [0.6-17.1] pg/mL, p < 0.01), whereas high mobility group protein B1 remained unchanged. IL-1α positively correlated with elevated bronchoalveolar lavage IL-8 levels (r(2) = 0.6095, p < 0.0001) and neutrophil percentage (r(2) = 0.25, p = 0.01). Conditioned media from P. aeruginosa infected epithelial cells induced a potent pro-inflammatory phenotype in fibroblasts via an IL-1α/IL-1R-dependent signaling pathway. In conclusion, we propose that IL-1α may be a novel therapeutic target to limit Pseudomonas associated allograft injury after lung transplantation.

AB - Bacterial infections after lung transplantation cause airway epithelial injury and are associated with an increased risk of developing bronchiolitis obliterans syndrome. The damaged epithelium is a source of alarmins that activate the innate immune system, yet their ability to activate fibroblasts in the development of bronchiolitis obliterans syndrome has not been evaluated. Two epithelial alarmins were measured longitudinally in bronchoalveolar lavages from lung transplant recipients who developed bronchiolitis obliterans syndrome and were compared to stable controls. In addition, conditioned media from human airway epithelial cells infected with Pseudomonas aeruginosa was applied to lung fibroblasts and inflammatory responses were determined. Interleukin-1 alpha (IL-1α) was increased in bronchoalveolar lavage of lung transplant recipients growing P. aeruginosa (11.5 [5.4-21.8] vs. 2.8 [0.9-9.4] pg/mL, p < 0.01) and was significantly elevated within 3 months of developing bronchiolitis obliterans syndrome (8.3 [1.4-25.1] vs. 3.6 [0.6-17.1] pg/mL, p < 0.01), whereas high mobility group protein B1 remained unchanged. IL-1α positively correlated with elevated bronchoalveolar lavage IL-8 levels (r(2) = 0.6095, p < 0.0001) and neutrophil percentage (r(2) = 0.25, p = 0.01). Conditioned media from P. aeruginosa infected epithelial cells induced a potent pro-inflammatory phenotype in fibroblasts via an IL-1α/IL-1R-dependent signaling pathway. In conclusion, we propose that IL-1α may be a novel therapeutic target to limit Pseudomonas associated allograft injury after lung transplantation.

U2 - 10.1111/ajt.13690

DO - 10.1111/ajt.13690

M3 - Article

C2 - 26714197

VL - 16

SP - 1751

EP - 1765

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 6

ER -