5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis

Abstract Monocyte chemoattractant protein-1 (MCP-1) plays an important role in initiating vascular inflammation; however, its cellular source in the injured vasculatures is unclear. Given the importance of high mobility group box 1 (HMGB1) in tissue injury, we investigated the role of vascular smoot...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jong Min Choi, Seung Eun Baek, Ji On Kim, Eun Yeong Jeon, Eun Jeong Jang, Chi Dae Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b04b639cf4841c29d45b5ee00d7ab62
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0b04b639cf4841c29d45b5ee00d7ab62
record_format	dspace
spelling	oai:doaj.org-article:0b04b639cf4841c29d45b5ee00d7ab622021-12-02T15:00:40Z5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis10.1038/s41598-021-90636-22045-2322https://doaj.org/article/0b04b639cf4841c29d45b5ee00d7ab622021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90636-2https://doaj.org/toc/2045-2322Abstract Monocyte chemoattractant protein-1 (MCP-1) plays an important role in initiating vascular inflammation; however, its cellular source in the injured vasculatures is unclear. Given the importance of high mobility group box 1 (HMGB1) in tissue injury, we investigated the role of vascular smooth muscle cells (VSMCs) in MCP-1 production in response to HMGB1. In primary cultured rat aortic VSMCs stimulated with HMGB1, the expression of MCP-1 and 5-lipoxygenase (LO) was increased. The increased MCP-1 expression in HMGB1 (30 ng/ml)-stimulated cells was significantly attenuated in 5-LO-deficient cells as well as in cells treated with zileuton, a 5-LO inhibitor. Likewise, MCP-1 expression and production were also increased in cells stimulated with exogenous leukotriene B4 (LTB4), but not exogenous LTC4. LTB4-induced MCP-1 expression was attenuated in cells treated with U75302, a LTB4 receptor 1 (BLTR1) inhibitor as well as in BLTR1-deficient cells, but not in 5-LO-deficient cells. Moreover, HMGB1-induced MCP-1 expression was attenuated in BLTR1-deficient cells or by treatment with a BLTR1 inhibitor, but not other leukotriene receptor inhibitors. In contrast to MCP-1 expression in response to LTB4, the increased MCP-1 production in HMGB1-stimulated VSMC was markedly attenuated in 5-LO-deficient cells, indicating a pivotal role of LTB4-BLTR1 signaling in MCP-1 expression in VSMCs. Taken together, 5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via BLTR1 signaling, suggesting the LTB4-BLTR1 signaling axis as a potential therapeutic target for vascular inflammation in the injured vasculatures.Jong Min ChoiSeung Eun BaekJi On KimEun Yeong JeonEun Jeong JangChi Dae KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jong Min Choi Seung Eun Baek Ji On Kim Eun Yeong Jeon Eun Jeong Jang Chi Dae Kim 5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis
description	Abstract Monocyte chemoattractant protein-1 (MCP-1) plays an important role in initiating vascular inflammation; however, its cellular source in the injured vasculatures is unclear. Given the importance of high mobility group box 1 (HMGB1) in tissue injury, we investigated the role of vascular smooth muscle cells (VSMCs) in MCP-1 production in response to HMGB1. In primary cultured rat aortic VSMCs stimulated with HMGB1, the expression of MCP-1 and 5-lipoxygenase (LO) was increased. The increased MCP-1 expression in HMGB1 (30 ng/ml)-stimulated cells was significantly attenuated in 5-LO-deficient cells as well as in cells treated with zileuton, a 5-LO inhibitor. Likewise, MCP-1 expression and production were also increased in cells stimulated with exogenous leukotriene B4 (LTB4), but not exogenous LTC4. LTB4-induced MCP-1 expression was attenuated in cells treated with U75302, a LTB4 receptor 1 (BLTR1) inhibitor as well as in BLTR1-deficient cells, but not in 5-LO-deficient cells. Moreover, HMGB1-induced MCP-1 expression was attenuated in BLTR1-deficient cells or by treatment with a BLTR1 inhibitor, but not other leukotriene receptor inhibitors. In contrast to MCP-1 expression in response to LTB4, the increased MCP-1 production in HMGB1-stimulated VSMC was markedly attenuated in 5-LO-deficient cells, indicating a pivotal role of LTB4-BLTR1 signaling in MCP-1 expression in VSMCs. Taken together, 5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via BLTR1 signaling, suggesting the LTB4-BLTR1 signaling axis as a potential therapeutic target for vascular inflammation in the injured vasculatures.
format	article
author	Jong Min Choi Seung Eun Baek Ji On Kim Eun Yeong Jeon Eun Jeong Jang Chi Dae Kim
author_facet	Jong Min Choi Seung Eun Baek Ji On Kim Eun Yeong Jeon Eun Jeong Jang Chi Dae Kim
author_sort	Jong Min Choi
title	5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis
title_short	5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis
title_full	5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis
title_fullStr	5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis
title_full_unstemmed	5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis
title_sort	5-lo-derived ltb4 plays a key role in mcp-1 expression in hmgb1-exposed vsmcs via a bltr1 signaling axis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0b04b639cf4841c29d45b5ee00d7ab62
work_keys_str_mv	AT jongminchoi 5loderivedltb4playsakeyroleinmcp1expressioninhmgb1exposedvsmcsviaabltr1signalingaxis AT seungeunbaek 5loderivedltb4playsakeyroleinmcp1expressioninhmgb1exposedvsmcsviaabltr1signalingaxis AT jionkim 5loderivedltb4playsakeyroleinmcp1expressioninhmgb1exposedvsmcsviaabltr1signalingaxis AT eunyeongjeon 5loderivedltb4playsakeyroleinmcp1expressioninhmgb1exposedvsmcsviaabltr1signalingaxis AT eunjeongjang 5loderivedltb4playsakeyroleinmcp1expressioninhmgb1exposedvsmcsviaabltr1signalingaxis AT chidaekim 5loderivedltb4playsakeyroleinmcp1expressioninhmgb1exposedvsmcsviaabltr1signalingaxis
_version_	1718389120318832640

5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis

Ejemplares similares