TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function

Abstract Oxylipins modulate the behavior of immune cells in inflammation. Soluble epoxide hydrolase (sEH) converts anti-inflammatory epoxyeicosatrienoic acid (EET) to dihydroxyeicosatrienoic acid (DHET). An sEH-inhibitor, TPPU, has been demonstrated to ameliorate lipopolysaccharide (LPS)- and sepsis...

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Autores principales:	Christian B. Bergmann, Bruce D. Hammock, Debin Wan, Falk Gogolla, Holly Goetzman, Charles C. Caldwell, Dorothy M. Supp
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6300e06abb654c439c3679971309bcfc
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spelling	oai:doaj.org-article:6300e06abb654c439c3679971309bcfc2021-12-02T18:51:42ZTPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function10.1038/s41598-021-96014-22045-2322https://doaj.org/article/6300e06abb654c439c3679971309bcfc2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96014-2https://doaj.org/toc/2045-2322Abstract Oxylipins modulate the behavior of immune cells in inflammation. Soluble epoxide hydrolase (sEH) converts anti-inflammatory epoxyeicosatrienoic acid (EET) to dihydroxyeicosatrienoic acid (DHET). An sEH-inhibitor, TPPU, has been demonstrated to ameliorate lipopolysaccharide (LPS)- and sepsis-induced inflammation via EETs. The immunomodulatory role of DHET is not well characterized. We hypothesized that TPPU dampens inflammation and that sEH-derived DHET alters neutrophil functionality in burn induced inflammation. Outbred mice were treated with vehicle, TPPU or 14,15-DHET and immediately subjected to either sham or dorsal scald 28% total body surface area burn injury. After 6 and 24 h, interleukin 6 (IL-6) serum levels and neutrophil activation were analyzed. For in vitro analyses, bone marrow derived neutrophil functionality and mRNA expression were examined. In vivo, 14,15-DHET and IL-6 serum concentrations were decreased after burn injury with TPPU administration. In vitro, 14,15-DHET impaired neutrophil chemotaxis, acidification, CXCR1/CXCR2 expression and reactive oxygen species (ROS) production, the latter independent from p38MAPK and PI3K signaling. We conclude that TPPU administration decreases DHET post-burn. Furthermore, DHET downregulates key neutrophil immune functions and mRNA expression. Altogether, these data reveal that TPPU not only increases anti-inflammatory and inflammation resolving EET levels, but also prevents potential impairment of neutrophils by DHET in trauma.Christian B. BergmannBruce D. HammockDebin WanFalk GogollaHolly GoetzmanCharles C. CaldwellDorothy M. SuppNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christian B. Bergmann Bruce D. Hammock Debin Wan Falk Gogolla Holly Goetzman Charles C. Caldwell Dorothy M. Supp TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function
description	Abstract Oxylipins modulate the behavior of immune cells in inflammation. Soluble epoxide hydrolase (sEH) converts anti-inflammatory epoxyeicosatrienoic acid (EET) to dihydroxyeicosatrienoic acid (DHET). An sEH-inhibitor, TPPU, has been demonstrated to ameliorate lipopolysaccharide (LPS)- and sepsis-induced inflammation via EETs. The immunomodulatory role of DHET is not well characterized. We hypothesized that TPPU dampens inflammation and that sEH-derived DHET alters neutrophil functionality in burn induced inflammation. Outbred mice were treated with vehicle, TPPU or 14,15-DHET and immediately subjected to either sham or dorsal scald 28% total body surface area burn injury. After 6 and 24 h, interleukin 6 (IL-6) serum levels and neutrophil activation were analyzed. For in vitro analyses, bone marrow derived neutrophil functionality and mRNA expression were examined. In vivo, 14,15-DHET and IL-6 serum concentrations were decreased after burn injury with TPPU administration. In vitro, 14,15-DHET impaired neutrophil chemotaxis, acidification, CXCR1/CXCR2 expression and reactive oxygen species (ROS) production, the latter independent from p38MAPK and PI3K signaling. We conclude that TPPU administration decreases DHET post-burn. Furthermore, DHET downregulates key neutrophil immune functions and mRNA expression. Altogether, these data reveal that TPPU not only increases anti-inflammatory and inflammation resolving EET levels, but also prevents potential impairment of neutrophils by DHET in trauma.
format	article
author	Christian B. Bergmann Bruce D. Hammock Debin Wan Falk Gogolla Holly Goetzman Charles C. Caldwell Dorothy M. Supp
author_facet	Christian B. Bergmann Bruce D. Hammock Debin Wan Falk Gogolla Holly Goetzman Charles C. Caldwell Dorothy M. Supp
author_sort	Christian B. Bergmann
title	TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function
title_short	TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function
title_full	TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function
title_fullStr	TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function
title_full_unstemmed	TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function
title_sort	tppu treatment of burned mice dampens inflammation and generation of bioactive dhet which impairs neutrophil function
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6300e06abb654c439c3679971309bcfc
work_keys_str_mv	AT christianbbergmann tpputreatmentofburnedmicedampensinflammationandgenerationofbioactivedhetwhichimpairsneutrophilfunction AT brucedhammock tpputreatmentofburnedmicedampensinflammationandgenerationofbioactivedhetwhichimpairsneutrophilfunction AT debinwan tpputreatmentofburnedmicedampensinflammationandgenerationofbioactivedhetwhichimpairsneutrophilfunction AT falkgogolla tpputreatmentofburnedmicedampensinflammationandgenerationofbioactivedhetwhichimpairsneutrophilfunction AT hollygoetzman tpputreatmentofburnedmicedampensinflammationandgenerationofbioactivedhetwhichimpairsneutrophilfunction AT charlesccaldwell tpputreatmentofburnedmicedampensinflammationandgenerationofbioactivedhetwhichimpairsneutrophilfunction AT dorothymsupp tpputreatmentofburnedmicedampensinflammationandgenerationofbioactivedhetwhichimpairsneutrophilfunction
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TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function

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