Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis

Emmet E. McGrath; Allan Lawrie; Helen M. Marriott; Paul Mercer; Simon S. Cross; Nadine Arnold; Vanessa Singleton; Alfred A. R. Thompson; Sarah R. Walmsley; Stephen A. Renshaw; Ian Sabroe; Rachel C. Chambers; David Dockrell; Moira K. B. Whyte

doi:10.1136/thoraxjnl-2011-200863

Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis

Emmet E. McGrath, Allan Lawrie, Helen M. Marriott, Paul Mercer, Simon S. Cross, Nadine Arnold, Vanessa Singleton, Alfred A. R. Thompson, Sarah R. Walmsley, Stephen A. Renshaw, Ian Sabroe, Rachel C. Chambers, David Dockrell, Moira K. B. Whyte^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Background The death receptor ligand tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) shows considerable clinical promise as a therapeutic agent. TRAIL induces leukocyte apoptosis, reducing acute inflammatory responses in the lung. It is not known whether TRAIL modifies chronic lung injury or whether TRAIL has a role in human idiopathic pulmonary fibrosis (IPF). We therefore explored the capacity of TRAIL to modify chronic inflammatory lung injury and studied TRAIL expression in patients with IPF.

Methods TRAIL(-/-) and wild-type mice were instilled with bleomycin and inflammation assessed at various time points by bronchoalveolar lavage and histology. Collagen deposition was measured by tissue hydroxyproline content. TRAIL expression in human IPF lung samples was assessed by immunohistochemistry and peripheral blood TRAIL measured by ELISA.

Results TRAIL(-/-) mice had an exaggerated delayed inflammatory response to bleomycin, with increased neutrophil numbers (mean 3.19 +/- 0.8 wild type vs 11.5 +/- 5.4x10(4) TRAIL(-/-), p

Conclusion These data suggest TRAIL may exert beneficial, anti-inflammatory actions in chronic pulmonary inflammation in murine models and that these mechanisms may be compromised in human IPF.

Original language	English
Pages (from-to)	796-803
Number of pages	8
Journal	Thorax
Volume	67
Issue number	9
DOIs	https://doi.org/10.1136/thoraxjnl-2011-200863
Publication status	Published - Sep 2012

Keywords

IDIOPATHIC PULMONARY-FIBROSIS
NEUTROPHIL APOPTOSIS
TRAIL
INFLAMMATION
EXPRESSION
MOUSE
CELLS
ATHEROSCLEROSIS
RESOLUTION
RECEPTORS

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10.1136/thoraxjnl-2011-200863

Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis
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http://thorax.bmj.com/content/67/9/796

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McGrath, E. E., Lawrie, A., Marriott, H. M., Mercer, P., Cross, S. S., Arnold, N., Singleton, V., Thompson, A. A. R., Walmsley, S. R., Renshaw, S. A., Sabroe, I., Chambers, R. C., Dockrell, D., & Whyte, M. K. B. (2012). Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis. Thorax, 67(9), 796-803. https://doi.org/10.1136/thoraxjnl-2011-200863

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title = "Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis",

abstract = "Background The death receptor ligand tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) shows considerable clinical promise as a therapeutic agent. TRAIL induces leukocyte apoptosis, reducing acute inflammatory responses in the lung. It is not known whether TRAIL modifies chronic lung injury or whether TRAIL has a role in human idiopathic pulmonary fibrosis (IPF). We therefore explored the capacity of TRAIL to modify chronic inflammatory lung injury and studied TRAIL expression in patients with IPF.Methods TRAIL(-/-) and wild-type mice were instilled with bleomycin and inflammation assessed at various time points by bronchoalveolar lavage and histology. Collagen deposition was measured by tissue hydroxyproline content. TRAIL expression in human IPF lung samples was assessed by immunohistochemistry and peripheral blood TRAIL measured by ELISA.Results TRAIL(-/-) mice had an exaggerated delayed inflammatory response to bleomycin, with increased neutrophil numbers (mean 3.19 +/- 0.8 wild type vs 11.5 +/- 5.4x10(4) TRAIL(-/-), pConclusion These data suggest TRAIL may exert beneficial, anti-inflammatory actions in chronic pulmonary inflammation in murine models and that these mechanisms may be compromised in human IPF.",

keywords = "IDIOPATHIC PULMONARY-FIBROSIS, NEUTROPHIL APOPTOSIS, TRAIL, INFLAMMATION, EXPRESSION, MOUSE, CELLS, ATHEROSCLEROSIS, RESOLUTION, RECEPTORS",

author = "McGrath, {Emmet E.} and Allan Lawrie and Marriott, {Helen M.} and Paul Mercer and Cross, {Simon S.} and Nadine Arnold and Vanessa Singleton and Thompson, {Alfred A. R.} and Walmsley, {Sarah R.} and Renshaw, {Stephen A.} and Ian Sabroe and Chambers, {Rachel C.} and David Dockrell and Whyte, {Moira K. B.}",

year = "2012",

month = sep,

doi = "10.1136/thoraxjnl-2011-200863",

language = "English",

volume = "67",

pages = "796--803",

journal = "Thorax",

issn = "0040-6376",

publisher = "BMJ Publishing Group",

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McGrath, EE, Lawrie, A, Marriott, HM, Mercer, P, Cross, SS, Arnold, N, Singleton, V, Thompson, AAR, Walmsley, SR, Renshaw, SA, Sabroe, I, Chambers, RC, Dockrell, D & Whyte, MKB 2012, 'Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis', Thorax, vol. 67, no. 9, pp. 796-803. https://doi.org/10.1136/thoraxjnl-2011-200863

TY - JOUR

T1 - Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis

AU - McGrath, Emmet E.

AU - Lawrie, Allan

AU - Marriott, Helen M.

AU - Mercer, Paul

AU - Cross, Simon S.

AU - Arnold, Nadine

AU - Singleton, Vanessa

AU - Thompson, Alfred A. R.

AU - Walmsley, Sarah R.

AU - Renshaw, Stephen A.

AU - Sabroe, Ian

AU - Chambers, Rachel C.

AU - Dockrell, David

AU - Whyte, Moira K. B.

PY - 2012/9

Y1 - 2012/9

N2 - Background The death receptor ligand tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) shows considerable clinical promise as a therapeutic agent. TRAIL induces leukocyte apoptosis, reducing acute inflammatory responses in the lung. It is not known whether TRAIL modifies chronic lung injury or whether TRAIL has a role in human idiopathic pulmonary fibrosis (IPF). We therefore explored the capacity of TRAIL to modify chronic inflammatory lung injury and studied TRAIL expression in patients with IPF.Methods TRAIL(-/-) and wild-type mice were instilled with bleomycin and inflammation assessed at various time points by bronchoalveolar lavage and histology. Collagen deposition was measured by tissue hydroxyproline content. TRAIL expression in human IPF lung samples was assessed by immunohistochemistry and peripheral blood TRAIL measured by ELISA.Results TRAIL(-/-) mice had an exaggerated delayed inflammatory response to bleomycin, with increased neutrophil numbers (mean 3.19 +/- 0.8 wild type vs 11.5 +/- 5.4x10(4) TRAIL(-/-), pConclusion These data suggest TRAIL may exert beneficial, anti-inflammatory actions in chronic pulmonary inflammation in murine models and that these mechanisms may be compromised in human IPF.

AB - Background The death receptor ligand tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) shows considerable clinical promise as a therapeutic agent. TRAIL induces leukocyte apoptosis, reducing acute inflammatory responses in the lung. It is not known whether TRAIL modifies chronic lung injury or whether TRAIL has a role in human idiopathic pulmonary fibrosis (IPF). We therefore explored the capacity of TRAIL to modify chronic inflammatory lung injury and studied TRAIL expression in patients with IPF.Methods TRAIL(-/-) and wild-type mice were instilled with bleomycin and inflammation assessed at various time points by bronchoalveolar lavage and histology. Collagen deposition was measured by tissue hydroxyproline content. TRAIL expression in human IPF lung samples was assessed by immunohistochemistry and peripheral blood TRAIL measured by ELISA.Results TRAIL(-/-) mice had an exaggerated delayed inflammatory response to bleomycin, with increased neutrophil numbers (mean 3.19 +/- 0.8 wild type vs 11.5 +/- 5.4x10(4) TRAIL(-/-), pConclusion These data suggest TRAIL may exert beneficial, anti-inflammatory actions in chronic pulmonary inflammation in murine models and that these mechanisms may be compromised in human IPF.

KW - IDIOPATHIC PULMONARY-FIBROSIS

KW - NEUTROPHIL APOPTOSIS

KW - TRAIL

KW - INFLAMMATION

KW - EXPRESSION

KW - MOUSE

KW - CELLS

KW - ATHEROSCLEROSIS

KW - RESOLUTION

KW - RECEPTORS

U2 - 10.1136/thoraxjnl-2011-200863

DO - 10.1136/thoraxjnl-2011-200863

M3 - Article

VL - 67

SP - 796

EP - 803

JO - Thorax

JF - Thorax

SN - 0040-6376

IS - 9

ER -

Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis

Abstract

Keywords

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