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Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia

(2010) JOURNAL OF IMMUNOLOGY. 185(7). p.4385-4392
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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.
Keywords
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

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Citation

Please use this url to cite or link to this publication:

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.
@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},
}

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