Journal article
HMGB1/IL-1 beta complexes in plasma microvesicles modulate immune responses to burn injury
PloS one, Vol.13(3), pp.e0195335-e0195335
03/30/2018
DOI: 10.1371/journal.pone.0195335
PMCID: PMC5877880
PMID: 29601597
Abstract
Modulating immune responses to sepsis and trauma remain one of the most difficult challenges in modern medicine. Large burn injuries (LBI) are a severe form of trauma associated with sepsis, immune impairment, and mortality. Immune dysfunction after LBI is complex, involving both enhanced and impaired immune activation. The release of Damage-Associated Molecular Patterns (DAMPs), such as HMGB1, and cytokines (e.g. IL-1 beta) creates an environment of immune dysfunction often leading to end organ failure and death. Both HMGB1 and IL-1 beta have been found to play critical roles in sepsis and post-burn immune dysfunction. HMGB1 and IL-1 beta have been shown previously to form potent complexes in vitro. We recently identified the presence of HMGB1/IL-1 beta heterocomplexes in human tissue. We now find HMGB1/IL-1 beta complexes in human and mouse plasma, and identify a synergistic role of HMGB1/IL-1 beta complexes in post-burn immune dysfunction. In both humans and mice, we found that HMGB1 was enriched in plasma microvesicles (MVs) after LBI. HMGB1 was found form complexes with IL-1 beta. Using flow cytometry of mouse plasma MVs, we identified an increase in an HMGB1+/IL-1 beta+ MVs. Using co-IP, HMGB1 was found to bind the pro-form of IL-1 beta in mouse and human plasma. Pro-IL-1 beta, which is traditionally considered inactive, became active when complexed with HMGB1. Human THP-1 monocytes treated with HMGB1-pro-IL-1 beta complexes showed increased transcription of LBI associated cytokines IL-6 and IFN beta along with suppression of iNOS, mimicking findings associated with LBI. These findings identify that HMGB1/IL-1 beta complexes released after burn injuries can modulate immune responses, and microvesicles are identified as a novel reservoir for these immune mediators. These complexes might serve as novel immune targets for the treatment of systemic immune responses due to LBI or other causes of sepsis.
Details
- Title: Subtitle
- HMGB1/IL-1 beta complexes in plasma microvesicles modulate immune responses to burn injury
- Creators
- Leon G. Coleman - University of North Carolina at Chapel HillRobert Maile - University of North Carolina at Chapel HillSamuel W. Jones - University of North Carolina at Chapel HillBruce A. Cairns - University of North Carolina at Chapel HillFulton T. Crews - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.13(3), pp.e0195335-e0195335
- DOI
- 10.1371/journal.pone.0195335
- PMID
- 29601597
- PMCID
- PMC5877880
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library Science
- Number of pages
- 23
- Grant note
- K08GM109106 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 2T32GM008450; K08GM109106 / NIGMS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) AA011605; AA020024 / NIAAA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA)
- Language
- English
- Date published
- 03/30/2018
- Academic Unit
- Surgery
- Record Identifier
- 9984756262302771
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