Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury

Acute lung injury (ALI) is characterized by alveolar damage, lung edema, and exacerbated inflammatory response. Growth arrest-specific protein 6 (Gas6) mediates many different functions, including cell survival, proliferation, inflammatory signaling, and apoptotic cell clearance (efferocytosis). The...

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Autores principales:	Bo-Min Kim, Ye-Ji Lee, Youn-Hee Choi, Eun-Mi Park, Jihee Lee Kang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Gas6 bleomycin inflammation apoptosis efferocytosis Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d66d2a931deb47958740b8271ae1fb1f
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spelling	oai:doaj.org-article:d66d2a931deb47958740b8271ae1fb1f2021-11-25T16:50:38ZGas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury10.3390/biomedicines91116742227-9059https://doaj.org/article/d66d2a931deb47958740b8271ae1fb1f2021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1674https://doaj.org/toc/2227-9059Acute lung injury (ALI) is characterized by alveolar damage, lung edema, and exacerbated inflammatory response. Growth arrest-specific protein 6 (Gas6) mediates many different functions, including cell survival, proliferation, inflammatory signaling, and apoptotic cell clearance (efferocytosis). The role of Gas6 in bleomycin (BLM)-induced ALI is unknown. We investigated whether exogenous administration of mouse recombinant Gas6 (rGas6) has anti-inflammatory and anti-apoptotic effects on BLM-induced ALI. Compared to mice treated with only BLM, the administration of rGas6 reduced the secretion of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2, and increased the secretion of hepatocyte growth factor in bronchoalveolar lavage (BAL) fluid. rGas6 administration also reduced BLM-induced inflammation and apoptosis as evidenced by reduced neutrophil recruitment into the lungs, total protein levels in BAL fluid, caspase-3 activity, and TUNEL-positive lung cells in lung tissue. Apoptotic cell clearance by alveolar macrophages was also enhanced in mice treated with both BLM and rGas6 compared with mice treated with only BLM. rGas6 also had pro-resolving and anti-apoptotic effects in mouse bone marrow-derived macrophages and alveolar epithelial cell lines stimulated with BLM in vitro. These findings indicate that rGas6 may play a protective role in BLM-induced ALI.Bo-Min KimYe-Ji LeeYoun-Hee ChoiEun-Mi ParkJihee Lee KangMDPI AGarticleGas6bleomycininflammationapoptosisefferocytosisBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1674, p 1674 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gas6 bleomycin inflammation apoptosis efferocytosis Biology (General) QH301-705.5
spellingShingle	Gas6 bleomycin inflammation apoptosis efferocytosis Biology (General) QH301-705.5 Bo-Min Kim Ye-Ji Lee Youn-Hee Choi Eun-Mi Park Jihee Lee Kang Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury
description	Acute lung injury (ALI) is characterized by alveolar damage, lung edema, and exacerbated inflammatory response. Growth arrest-specific protein 6 (Gas6) mediates many different functions, including cell survival, proliferation, inflammatory signaling, and apoptotic cell clearance (efferocytosis). The role of Gas6 in bleomycin (BLM)-induced ALI is unknown. We investigated whether exogenous administration of mouse recombinant Gas6 (rGas6) has anti-inflammatory and anti-apoptotic effects on BLM-induced ALI. Compared to mice treated with only BLM, the administration of rGas6 reduced the secretion of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2, and increased the secretion of hepatocyte growth factor in bronchoalveolar lavage (BAL) fluid. rGas6 administration also reduced BLM-induced inflammation and apoptosis as evidenced by reduced neutrophil recruitment into the lungs, total protein levels in BAL fluid, caspase-3 activity, and TUNEL-positive lung cells in lung tissue. Apoptotic cell clearance by alveolar macrophages was also enhanced in mice treated with both BLM and rGas6 compared with mice treated with only BLM. rGas6 also had pro-resolving and anti-apoptotic effects in mouse bone marrow-derived macrophages and alveolar epithelial cell lines stimulated with BLM in vitro. These findings indicate that rGas6 may play a protective role in BLM-induced ALI.
format	article
author	Bo-Min Kim Ye-Ji Lee Youn-Hee Choi Eun-Mi Park Jihee Lee Kang
author_facet	Bo-Min Kim Ye-Ji Lee Youn-Hee Choi Eun-Mi Park Jihee Lee Kang
author_sort	Bo-Min Kim
title	Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury
title_short	Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury
title_full	Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury
title_fullStr	Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury
title_full_unstemmed	Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury
title_sort	gas6 ameliorates inflammatory response and apoptosis in bleomycin-induced acute lung injury
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d66d2a931deb47958740b8271ae1fb1f
work_keys_str_mv	AT bominkim gas6amelioratesinflammatoryresponseandapoptosisinbleomycininducedacutelunginjury AT yejilee gas6amelioratesinflammatoryresponseandapoptosisinbleomycininducedacutelunginjury AT younheechoi gas6amelioratesinflammatoryresponseandapoptosisinbleomycininducedacutelunginjury AT eunmipark gas6amelioratesinflammatoryresponseandapoptosisinbleomycininducedacutelunginjury AT jiheeleekang gas6amelioratesinflammatoryresponseandapoptosisinbleomycininducedacutelunginjury
_version_	1718412928075431936

Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury

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