Oxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.

High mobility group box 1 (HMGB1) is a nuclear transcription factor. Once HMGB1 is released by damaged cells or activated immune cells, it acts as danger molecule and triggers the inflammatory signaling cascade. Currently, evidence is accumulating that posttranslational modifications such as oxidati...

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Autores principales:	Anding Liu, Haoshu Fang, Olaf Dirsch, Hao Jin, Uta Dahmen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/635e188b500d45dc8bd72a811c79a720
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spelling	oai:doaj.org-article:635e188b500d45dc8bd72a811c79a7202021-11-18T07:22:09ZOxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.1932-620310.1371/journal.pone.0035379https://doaj.org/article/635e188b500d45dc8bd72a811c79a7202012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22514737/?tool=EBIhttps://doaj.org/toc/1932-6203High mobility group box 1 (HMGB1) is a nuclear transcription factor. Once HMGB1 is released by damaged cells or activated immune cells, it acts as danger molecule and triggers the inflammatory signaling cascade. Currently, evidence is accumulating that posttranslational modifications such as oxidation may modulate the pro-inflammatory potential of danger signals. We hypothesized that oxidation of HMGB1 may reduce its pro-inflammatory potential and could take place during prolonged ischemia and upon reperfusion.Liver grafts were cold preserved for 24 h and flushed with saline in hourly intervals to collect the effluent. Liver grafts, cold-preserved for 6 h, were transplanted into syngeneic recipients to obtain serum and liver samples 24 h after initiation of reperfusion. Addition of the effluent to a macrophage culture induced the synthesis of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. The stimulatory activity of graft effluent was reduced after depletion of HMGB1 via immunoprecipitation. Oxidation of the effluent HMGB1 using H(2)O(2) attenuated its stimulatory activity as well. Liver transplantation of cold preserved grafts caused HMGB1 translocation and release as determined by immunohistochemistry and ELISA-assay, respectively. Using Western blot with non-reducing conditions revealed the presence of oxidized HMGB1 in liver samples obtained after 12 h and in effluent samples after 16 h of cold preservation as well as in liver and serum samples obtained 24 h after reperfusion.These observations confirm that post-translational oxidation of HMGB1 attenuates its pro-inflammatory activity. Oxidation of HMGB1 as induced during prolonged ischemia and by reoxygenation during reperfusion in vivo might also attenuate its pro-inflammatory activity. Our findings also call for future studies to investigate the mechanism of the inhibitory effect of oxidized HMGB1 on the pro-inflammatory potential.Anding LiuHaoshu FangOlaf DirschHao JinUta DahmenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35379 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anding Liu Haoshu Fang Olaf Dirsch Hao Jin Uta Dahmen Oxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.
description	High mobility group box 1 (HMGB1) is a nuclear transcription factor. Once HMGB1 is released by damaged cells or activated immune cells, it acts as danger molecule and triggers the inflammatory signaling cascade. Currently, evidence is accumulating that posttranslational modifications such as oxidation may modulate the pro-inflammatory potential of danger signals. We hypothesized that oxidation of HMGB1 may reduce its pro-inflammatory potential and could take place during prolonged ischemia and upon reperfusion.Liver grafts were cold preserved for 24 h and flushed with saline in hourly intervals to collect the effluent. Liver grafts, cold-preserved for 6 h, were transplanted into syngeneic recipients to obtain serum and liver samples 24 h after initiation of reperfusion. Addition of the effluent to a macrophage culture induced the synthesis of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. The stimulatory activity of graft effluent was reduced after depletion of HMGB1 via immunoprecipitation. Oxidation of the effluent HMGB1 using H(2)O(2) attenuated its stimulatory activity as well. Liver transplantation of cold preserved grafts caused HMGB1 translocation and release as determined by immunohistochemistry and ELISA-assay, respectively. Using Western blot with non-reducing conditions revealed the presence of oxidized HMGB1 in liver samples obtained after 12 h and in effluent samples after 16 h of cold preservation as well as in liver and serum samples obtained 24 h after reperfusion.These observations confirm that post-translational oxidation of HMGB1 attenuates its pro-inflammatory activity. Oxidation of HMGB1 as induced during prolonged ischemia and by reoxygenation during reperfusion in vivo might also attenuate its pro-inflammatory activity. Our findings also call for future studies to investigate the mechanism of the inhibitory effect of oxidized HMGB1 on the pro-inflammatory potential.
format	article
author	Anding Liu Haoshu Fang Olaf Dirsch Hao Jin Uta Dahmen
author_facet	Anding Liu Haoshu Fang Olaf Dirsch Hao Jin Uta Dahmen
author_sort	Anding Liu
title	Oxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.
title_short	Oxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.
title_full	Oxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.
title_fullStr	Oxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.
title_full_unstemmed	Oxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.
title_sort	oxidation of hmgb1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/635e188b500d45dc8bd72a811c79a720
work_keys_str_mv	AT andingliu oxidationofhmgb1causesattenuationofitsproinflammatoryactivityandoccursduringliverischemiaandreperfusion AT haoshufang oxidationofhmgb1causesattenuationofitsproinflammatoryactivityandoccursduringliverischemiaandreperfusion AT olafdirsch oxidationofhmgb1causesattenuationofitsproinflammatoryactivityandoccursduringliverischemiaandreperfusion AT haojin oxidationofhmgb1causesattenuationofitsproinflammatoryactivityandoccursduringliverischemiaandreperfusion AT utadahmen oxidationofhmgb1causesattenuationofitsproinflammatoryactivityandoccursduringliverischemiaandreperfusion
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Oxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.

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