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Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia

Mohamed Lamkanfi UGent, Anasuya Sarkar, Lieselotte Vande Walle UGent, Alberto C Vitari, mal AO Amer, Mark D Wewers, Kevin J Tracey, Thirumala-Devi Kanneganti and Vishva M Dixit (2010) JOURNAL OF IMMUNOLOGY. 185(7). p.4385-4392
abstract
Abstract: Endotoxin administration recapitulates many of the host responses to sepsis. Inhibitors of the cysteine protease caspase 1 have long been sought as a therapeutic because mice lacking caspase 1 are resistant to LPS-induced endotoxic shock. According to current thinking, caspase 1-mediated shock requires the proinflammatory caspase 1 substrates IL-1 beta and IL-18. We show, however, that mice lacking both IL-1b and IL-18 are normally susceptible to LPS-induced splenocyte apoptosis and endotoxic shock. This finding indicates the existence of another caspase 1-dependent mediator of endotoxemia. Reduced serum high mobility group box 1 (HMGB1) levels in caspase 1-deficient mice correlated with their resistance to LPS. A critical role for HMGB1 in endotoxemia was confirmed when mice deficient for IL-1 beta and IL-18 were protected from a lethal dose of LPS by pretreatment with HMGB1-neutralizing Abs. We found that HMGB1 secretion from LPS-primed macrophages required the inflammasome components apoptotic speck protein containing a caspase activation and recruitment domain (ASC), caspase 1 and Nalp3, whereas HMGB1 secretion from macrophages infected in vitro with Salmonella typhimurium was dependent on caspase 1 and Ipaf. Thus, HMGB1 secretion, which is critical for endotoxemia, occurs downstream of inflammasome assembly and caspase 1 activation.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
APOPTOSIS, IN-VIVO, PROTEIN HMGB1, NALP3 INFLAMMASOME, PROINFLAMMATORY ACTIVITY, INTERLEUKIN-1-BETA CONVERTING-ENZYME, MOBILITY GROUP BOX-1, CASPASE-1 ACTIVATION, MICE DEFICIENT, RECOMBINANT HMGB1
journal title
JOURNAL OF IMMUNOLOGY
J. Immunol.
volume
185
issue
7
pages
4385 - 4392
Web of Science type
Article
Web of Science id
000282059500066
JCR category
IMMUNOLOGY
JCR impact factor
5.745 (2010)
JCR rank
20/133 (2010)
JCR quartile
1 (2010)
ISSN
0022-1767
DOI
10.4049/jimmunol.1000803
language
English
UGent publication?
yes
classification
A1
additional info
addendum published as 'HMGB1 release by inflammasomes' in Virulence (2011) 2(2), 162-165 (DOI: 10.4161/viru.2.2.15480)
copyright statement
I have transferred the copyright for this publication to the publisher
id
1055935
handle
http://hdl.handle.net/1854/LU-1055935
date created
2010-10-08 14:44:34
date last changed
2016-12-19 15:44:33
@article{1055935,
  abstract     = {Abstract: Endotoxin administration recapitulates many of the host responses to sepsis. Inhibitors of the cysteine protease caspase 1 have long been sought as a therapeutic because mice lacking caspase 1 are resistant to LPS-induced endotoxic shock. According to current thinking, caspase 1-mediated shock requires the proinflammatory caspase 1 substrates IL-1 beta and IL-18. We show, however, that mice lacking both IL-1b and IL-18 are normally susceptible to LPS-induced splenocyte apoptosis and endotoxic shock. This finding indicates the existence of another caspase 1-dependent mediator of endotoxemia. Reduced serum high mobility group box 1 (HMGB1) levels in caspase 1-deficient mice correlated with their resistance to LPS. A critical role for HMGB1 in endotoxemia was confirmed when mice deficient for IL-1 beta and IL-18 were protected from a lethal dose of LPS by pretreatment with HMGB1-neutralizing Abs. We found that HMGB1 secretion from LPS-primed macrophages required the inflammasome components apoptotic speck protein containing a caspase activation and recruitment domain (ASC), caspase 1 and Nalp3, whereas HMGB1 secretion from macrophages infected in vitro with Salmonella typhimurium was dependent on caspase 1 and Ipaf. Thus, HMGB1 secretion, which is critical for endotoxemia, occurs downstream of inflammasome assembly and caspase 1 activation.},
  author       = {Lamkanfi, Mohamed and Sarkar, Anasuya and Vande Walle, Lieselotte and Vitari, Alberto C and Amer, mal AO and Wewers, Mark D and Tracey, Kevin J and Kanneganti, Thirumala-Devi and Dixit, Vishva M},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  keyword      = {APOPTOSIS,IN-VIVO,PROTEIN HMGB1,NALP3 INFLAMMASOME,PROINFLAMMATORY ACTIVITY,INTERLEUKIN-1-BETA CONVERTING-ENZYME,MOBILITY GROUP BOX-1,CASPASE-1 ACTIVATION,MICE DEFICIENT,RECOMBINANT HMGB1},
  language     = {eng},
  number       = {7},
  pages        = {4385--4392},
  title        = {Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia},
  url          = {http://dx.doi.org/10.4049/jimmunol.1000803},
  volume       = {185},
  year         = {2010},
}

Chicago
Lamkanfi, Mohamed, Anasuya Sarkar, Lieselotte Vande Walle, Alberto C Vitari, mal AO Amer, Mark D Wewers, Kevin J Tracey, Thirumala-Devi Kanneganti, and Vishva M Dixit. 2010. “Inflammasome-dependent Release of the Alarmin HMGB1 in Endotoxemia.” Journal of Immunology 185 (7): 4385–4392.
APA
Lamkanfi, M., Sarkar, A., Vande Walle, L., Vitari, A. C., Amer, mal A., Wewers, M. D., Tracey, K. J., et al. (2010). Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia. JOURNAL OF IMMUNOLOGY, 185(7), 4385–4392.
Vancouver
1.
Lamkanfi M, Sarkar A, Vande Walle L, Vitari AC, Amer mal A, Wewers MD, et al. Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia. JOURNAL OF IMMUNOLOGY. 2010;185(7):4385–92.
MLA
Lamkanfi, Mohamed, Anasuya Sarkar, Lieselotte Vande Walle, et al. “Inflammasome-dependent Release of the Alarmin HMGB1 in Endotoxemia.” JOURNAL OF IMMUNOLOGY 185.7 (2010): 4385–4392. Print.