The heme oxygenase-1 inducer THI-56 negatively regulates iNOS expression and HMGB1 release in LPS-activated RAW 264.7 cells and CLP-induced septic mice.

The nuclear DNA binding protein high mobility group box 1 (HMGB1) has recently been suggested to act as a late mediator of septic shock. The effect of ((S)-6,7-dihydroxy-1-(4-hydroxynaphthylmethyl)-1,2,3,4-tetrahydroisoquinoline alkaloid, also known as THI-56, in an experimental model of sepsis was...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Eun Jung Park, Hwa Jin Jang, Konstantin Tsoyi, Young Min Kim, Sang Won Park, Hye Jung Kim, Jae Heun Lee, Ki Churl Chang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4ed68cd66c194bc5b4d4e1bf98d777b7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4ed68cd66c194bc5b4d4e1bf98d777b7
record_format	dspace
spelling	oai:doaj.org-article:4ed68cd66c194bc5b4d4e1bf98d777b72021-11-18T08:52:38ZThe heme oxygenase-1 inducer THI-56 negatively regulates iNOS expression and HMGB1 release in LPS-activated RAW 264.7 cells and CLP-induced septic mice.1932-620310.1371/journal.pone.0076293https://doaj.org/article/4ed68cd66c194bc5b4d4e1bf98d777b72013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24098466/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The nuclear DNA binding protein high mobility group box 1 (HMGB1) has recently been suggested to act as a late mediator of septic shock. The effect of ((S)-6,7-dihydroxy-1-(4-hydroxynaphthylmethyl)-1,2,3,4-tetrahydroisoquinoline alkaloid, also known as THI-56, in an experimental model of sepsis was investigated. THI-56 exhibited potent anti-inflammatory properties in response to LPS in RAW 264.7 cells. In particular, THI-56 significantly inhibited the expression of inducible nitric oxide synthase (iNOS) and the release of HMGB1 in activated macrophages. THI-56 activated NE-F2-regulated factor 2 (Nrf-2)/heme oxygenase 1 (HO-1). The specific knockdown of the HO-1 gene by HO-1 siRNA significantly reversed the inhibitory effects of THI-56 on iNOS expression and HMGB1 release in LPS-stimulated macrophages. Importantly, THI-56 administration protected animals from death induced by either a lethal dose of LPS or cecal ligation and puncture (CLP). Furthermore, the ALT, AST, BUN, creatinine, and HMGB1 levels in the blood were significantly increased in CLP-induced septic mice, and the administration of THI-56 reduced these levels in a concentration-dependent and zinc protoporphyrin IX (ZnPPIX)-sensitive manner. In addition, the administration of THI-56 significantly ameliorated not only lung damage but also macrophage infiltration in the livers of CLP-induced septic mice, and these effects were also abrogated in the presence of ZnPPIX. Thus, we conclude that THI-56 significantly attenuates the proinflammatory response induced by LPS and reduces organ damage in a CLP-induced sepsis model through the upregulation of Nrf-2/HO-1.Eun Jung ParkHwa Jin JangKonstantin TsoyiYoung Min KimSang Won ParkHye Jung KimJae Heun LeeKi Churl ChangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e76293 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eun Jung Park Hwa Jin Jang Konstantin Tsoyi Young Min Kim Sang Won Park Hye Jung Kim Jae Heun Lee Ki Churl Chang The heme oxygenase-1 inducer THI-56 negatively regulates iNOS expression and HMGB1 release in LPS-activated RAW 264.7 cells and CLP-induced septic mice.
description	The nuclear DNA binding protein high mobility group box 1 (HMGB1) has recently been suggested to act as a late mediator of septic shock. The effect of ((S)-6,7-dihydroxy-1-(4-hydroxynaphthylmethyl)-1,2,3,4-tetrahydroisoquinoline alkaloid, also known as THI-56, in an experimental model of sepsis was investigated. THI-56 exhibited potent anti-inflammatory properties in response to LPS in RAW 264.7 cells. In particular, THI-56 significantly inhibited the expression of inducible nitric oxide synthase (iNOS) and the release of HMGB1 in activated macrophages. THI-56 activated NE-F2-regulated factor 2 (Nrf-2)/heme oxygenase 1 (HO-1). The specific knockdown of the HO-1 gene by HO-1 siRNA significantly reversed the inhibitory effects of THI-56 on iNOS expression and HMGB1 release in LPS-stimulated macrophages. Importantly, THI-56 administration protected animals from death induced by either a lethal dose of LPS or cecal ligation and puncture (CLP). Furthermore, the ALT, AST, BUN, creatinine, and HMGB1 levels in the blood were significantly increased in CLP-induced septic mice, and the administration of THI-56 reduced these levels in a concentration-dependent and zinc protoporphyrin IX (ZnPPIX)-sensitive manner. In addition, the administration of THI-56 significantly ameliorated not only lung damage but also macrophage infiltration in the livers of CLP-induced septic mice, and these effects were also abrogated in the presence of ZnPPIX. Thus, we conclude that THI-56 significantly attenuates the proinflammatory response induced by LPS and reduces organ damage in a CLP-induced sepsis model through the upregulation of Nrf-2/HO-1.
format	article
author	Eun Jung Park Hwa Jin Jang Konstantin Tsoyi Young Min Kim Sang Won Park Hye Jung Kim Jae Heun Lee Ki Churl Chang
author_facet	Eun Jung Park Hwa Jin Jang Konstantin Tsoyi Young Min Kim Sang Won Park Hye Jung Kim Jae Heun Lee Ki Churl Chang
author_sort	Eun Jung Park
title	The heme oxygenase-1 inducer THI-56 negatively regulates iNOS expression and HMGB1 release in LPS-activated RAW 264.7 cells and CLP-induced septic mice.
title_short	The heme oxygenase-1 inducer THI-56 negatively regulates iNOS expression and HMGB1 release in LPS-activated RAW 264.7 cells and CLP-induced septic mice.
title_full	The heme oxygenase-1 inducer THI-56 negatively regulates iNOS expression and HMGB1 release in LPS-activated RAW 264.7 cells and CLP-induced septic mice.
title_fullStr	The heme oxygenase-1 inducer THI-56 negatively regulates iNOS expression and HMGB1 release in LPS-activated RAW 264.7 cells and CLP-induced septic mice.
title_full_unstemmed	The heme oxygenase-1 inducer THI-56 negatively regulates iNOS expression and HMGB1 release in LPS-activated RAW 264.7 cells and CLP-induced septic mice.
title_sort	heme oxygenase-1 inducer thi-56 negatively regulates inos expression and hmgb1 release in lps-activated raw 264.7 cells and clp-induced septic mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4ed68cd66c194bc5b4d4e1bf98d777b7
work_keys_str_mv	AT eunjungpark thehemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT hwajinjang thehemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT konstantintsoyi thehemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT youngminkim thehemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT sangwonpark thehemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT hyejungkim thehemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT jaeheunlee thehemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT kichurlchang thehemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT eunjungpark hemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT hwajinjang hemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT konstantintsoyi hemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT youngminkim hemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT sangwonpark hemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT hyejungkim hemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT jaeheunlee hemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice AT kichurlchang hemeoxygenase1inducerthi56negativelyregulatesinosexpressionandhmgb1releaseinlpsactivatedraw2647cellsandclpinducedsepticmice
_version_	1718421199413837824

The heme oxygenase-1 inducer THI-56 negatively regulates iNOS expression and HMGB1 release in LPS-activated RAW 264.7 cells and CLP-induced septic mice.

Ejemplares similares