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Surfactant protein D deficiency aggravates cigarette smoke-induced lung inflammation by upregulation of ceramide synthesis

Surfactant protein D deficiency aggravates cigarette smoke-induced lung inflammation by upregulation of ceramide synthesis
Surfactant protein D deficiency aggravates cigarette smoke-induced lung inflammation by upregulation of ceramide synthesis
Cigarette smoke (CS) is the main cause of chronic obstructive pulmonary disease. Surfactant protein D (SP-D) is an important anti-inflammatory protein that regulates host immune defense in the lungs. Here, we investigated the role of SP-D in a murine model of CS-induced inflammation. Pulmonary SP-D localization and abundance was compared between smoker and non-smoker individuals. For in vivo studies, wildtype, and SP-D-deficient mice were exposed to CS for either 12 weeks or 3 days. Moreover, the effect of therapeutic administration of recombinant fragment of human SP-D on the acute CS-induced changes was evaluated. Pulmonary SP-D appeared with heterogenous expression in human smokers, while mouse lung SP-D was uniformly upregulated after CS exposure. We found that SP-D-deficient mice were more susceptible to CS-induced macrophage-rich airway inflammation. SP-D deficiency influenced local pro-inflammatory cytokine levels, with increased CCL3 and interleukin-6 but decreased CXCL1. Furthermore, CS exposure caused significant upregulation of pro-inflammatory ceramides and related ceramide synthase gene transcripts in SP-D-deficient mice compared to wildtype littermates. Administration of recombinant fragment of human SP-D (rfhSP-D) alleviated CS-induced macrophage infiltration and prevented induction of ceramide synthase gene expression. Finally, rfhSP-D treatment attenuated CS-induced human epithelial cell apoptosis in vitro. Our results indicate that SP-D deficiency aggravates CS-induced lung inflammation partly through regulation of ceramide synthesis and that local SP-D enrichment rescues CS-induced inflammation.
1664-3224
Pilecki, Bartosz
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Wulf-Johansson, Helle
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Støttrup, Christian
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Troest Jørgensen, Patricia
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Djiadeu, Pascal
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Bathum Nexøe, Anders
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Schlosser, Anders
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Hansen, Søren Werner Karlskov
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Madsen, Jens
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Clark, Howard
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Nielsen, Claus
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Vestbo, Jorgen
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Palaniyar, Nades
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Holmskov, Uffe
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Sorensen, Grith Lykke
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Pilecki, Bartosz
2a7baa70-6251-41ab-9509-4b171cdfb9b0
Wulf-Johansson, Helle
32088471-a56b-481f-b80a-30548a1456b9
Støttrup, Christian
b2ddb54f-8c71-4113-960d-5cb525dc0e4d
Troest Jørgensen, Patricia
355dea34-642b-4eaa-8914-aa2eb406dee0
Djiadeu, Pascal
e6068165-1b02-4516-bb28-2bd178d2b512
Bathum Nexøe, Anders
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Schlosser, Anders
37911406-2ff0-4ef1-9f01-c03576a9dd98
Hansen, Søren Werner Karlskov
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Madsen, Jens
b5d8ae35-00ac-4d19-930e-d8ddec497359
Clark, Howard
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Nielsen, Claus
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Vestbo, Jorgen
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Palaniyar, Nades
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Holmskov, Uffe
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Sorensen, Grith Lykke
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Pilecki, Bartosz, Wulf-Johansson, Helle, Støttrup, Christian, Troest Jørgensen, Patricia, Djiadeu, Pascal, Bathum Nexøe, Anders, Schlosser, Anders, Hansen, Søren Werner Karlskov, Madsen, Jens, Clark, Howard, Nielsen, Claus, Vestbo, Jorgen, Palaniyar, Nades, Holmskov, Uffe and Sorensen, Grith Lykke (2018) Surfactant protein D deficiency aggravates cigarette smoke-induced lung inflammation by upregulation of ceramide synthesis. Frontiers in Immunology, [3013]. (doi:10.3389/fimmu.2018.03013).

Record type: Article

Abstract

Cigarette smoke (CS) is the main cause of chronic obstructive pulmonary disease. Surfactant protein D (SP-D) is an important anti-inflammatory protein that regulates host immune defense in the lungs. Here, we investigated the role of SP-D in a murine model of CS-induced inflammation. Pulmonary SP-D localization and abundance was compared between smoker and non-smoker individuals. For in vivo studies, wildtype, and SP-D-deficient mice were exposed to CS for either 12 weeks or 3 days. Moreover, the effect of therapeutic administration of recombinant fragment of human SP-D on the acute CS-induced changes was evaluated. Pulmonary SP-D appeared with heterogenous expression in human smokers, while mouse lung SP-D was uniformly upregulated after CS exposure. We found that SP-D-deficient mice were more susceptible to CS-induced macrophage-rich airway inflammation. SP-D deficiency influenced local pro-inflammatory cytokine levels, with increased CCL3 and interleukin-6 but decreased CXCL1. Furthermore, CS exposure caused significant upregulation of pro-inflammatory ceramides and related ceramide synthase gene transcripts in SP-D-deficient mice compared to wildtype littermates. Administration of recombinant fragment of human SP-D (rfhSP-D) alleviated CS-induced macrophage infiltration and prevented induction of ceramide synthase gene expression. Finally, rfhSP-D treatment attenuated CS-induced human epithelial cell apoptosis in vitro. Our results indicate that SP-D deficiency aggravates CS-induced lung inflammation partly through regulation of ceramide synthesis and that local SP-D enrichment rescues CS-induced inflammation.

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Pilecki 2018 - Version of Record
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Accepted/In Press date: 5 December 2018
e-pub ahead of print date: 18 December 2018
Published date: 18 December 2018

Identifiers

Local EPrints ID: 427178
URI: http://eprints.soton.ac.uk/id/eprint/427178
ISSN: 1664-3224
PURE UUID: bdc9aed8-e1a4-4615-a56a-0a3926a13e23
ORCID for Jens Madsen: ORCID iD orcid.org/0000-0003-1664-7645

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Date deposited: 04 Jan 2019 17:30
Last modified: 22 Nov 2021 02:56

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Contributors

Author: Bartosz Pilecki
Author: Helle Wulf-Johansson
Author: Christian Støttrup
Author: Patricia Troest Jørgensen
Author: Pascal Djiadeu
Author: Anders Bathum Nexøe
Author: Anders Schlosser
Author: Søren Werner Karlskov Hansen
Author: Jens Madsen ORCID iD
Author: Howard Clark
Author: Claus Nielsen
Author: Jorgen Vestbo
Author: Nades Palaniyar
Author: Uffe Holmskov
Author: Grith Lykke Sorensen

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